V. A. Alvarez and B. L. Sabatini, Anatomical and Physiological Plasticity of Dendritic Spines, Annu. Rev. Neurosci, vol.30, pp.79-97, 2007.

W. W. Anderson and G. L. Collingridge, The LTP Program: a data acquisition program for on-line analysis of long-term potentiation and other synaptic events, J. Neurosci. Methods, vol.108, pp.71-83, 2001.

V. Blanchard, S. Moussaoui, C. Czech, N. Touchet, B. Bonici et al., Time sequence of maturation of dystrophic neurites associated with Abeta deposits in APP/PS1 transgenic mice, Exp. Neurol, vol.184, pp.247-263, 2003.

H. Breyhan, O. Wirths, K. Duan, A. Marcello, J. Rettig et al., , 2009.

, APP/PS1KI bigenic mice develop early synaptic deficits and hippocampus atrophy, Acta Neuropathol. (Berl.), vol.117, pp.677-685

C. Casas, N. Sergeant, J. Itier, V. Blanchard, O. Wirths et al., Massive CA1/2 neuronal loss with intraneuronal and N-terminal truncated Abeta42 accumulation in a novel Alzheimer transgenic model, Am. J. Pathol, vol.165, pp.1289-1300, 2004.

C. A. Davies, D. M. Mann, P. Q. Sumpter, and P. O. Yates, A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease, J. Neurol. Sci, vol.78, pp.151-164, 1987.

S. T. Dekosky and S. W. Scheff, Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity, Ann. Neurol, vol.27, pp.457-464, 1990.

C. Duyckaerts, B. Delatour, and M. Potier, Classification and basic pathology of Alzheimer disease, Acta Neuropathol. (Berl.), vol.118, pp.5-36, 2009.

B. Efron, Better Bootstrap Confidence Intervals, J. Am. Stat. Assoc, vol.82, pp.171-185, 1987.

A. Faure, L. Verret, B. Bozon, N. El-tannir-el-tayara, M. Ly et al., Impaired neurogenesis, neuronal loss, and brain functional deficits in the APPxPS1-Ki mouse model of Alzheimer's disease, Neurobiol. Aging, vol.32, pp.407-418, 2011.

J. C. Fiala, Reconstruct: a free editor for serial section microscopy, J. Microsc, vol.218, pp.52-61, 2005.

J. C. Fiala, J. Spacek, and K. M. Harris, Chapter 1 : Dendrite structure, pp.1-40, 2008.

E. Fifková and R. J. Delay, Cytoplasmic actin in neuronal processes as a possible mediator of synaptic plasticity, J. Cell Biol, vol.95, pp.345-350, 1982.

Y. Gerakis and C. Hetz, Emerging roles of ER stress in the aetiology and pathogenesis of Alzheimer's disease, FEBS J, p.142, 2017.

H. J. Gundersen, T. F. Bendtsen, L. Korbo, N. Marcussen, A. Møller et al., Some new, simple and efficient stereological methods and their use in pathological research and diagnosis, APMIS Acta Pathol. Microbiol. Immunol. Scand, vol.96, pp.379-394, 1988.

K. H. El-hachimi and J. F. Foncin, , 1990.

, C. R. Acad. Sci. III, vol.311, pp.397-402

K. H. El-hachimi, L. Verga, G. Giaccone, F. Tagliavini, B. Frangione et al., Relationship between non-fibrillary amyloid precursors and cell processes in the cortical neuropil of Alzheimer patients, Neurosci. Lett, vol.129, pp.119-122, 1991.

K. M. Harris and J. K. Stevens, Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics, J. Neurosci, vol.9, pp.2982-2997, 1989.

K. M. Harris, F. E. Jensen, and B. Tsao, Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation, J Neurosci, vol.12, issue.8, 1992.

, J. Neurosci, vol.12, pp.2685-2705

M. L. Hines and N. T. Carnevale, The NEURON simulation environment, Neural Comput, vol.9, pp.1179-1209, 1997.

S. Horellou, O. Pascual, A. Triller, M. , and S. , Adaptive and non-adaptive changes in activity-deprived presynaptic terminals, Eur. J. Neurosci, vol.39, pp.61-71, 2014.

H. Hsieh, J. Boehm, C. Sato, T. Iwatsubo, T. Tomita et al., , 2006.

, AMPAR Removal Underlies A?-Induced Synaptic Depression and Dendritic Spine Loss, Neuron, vol.52, pp.831-843

R. L. Huganir and R. A. Nicoll, AMPARs and Synaptic Plasticity: The Last 25 Years, Neuron, vol.80, pp.704-717, 2013.

J. S. Jacobsen, C. Wu, J. M. Redwine, T. A. Comery, R. Arias et al., Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease, Proc. Natl. Acad. Sci. U. S. A, vol.103, pp.5161-5166, 2006.

T. Jonsson, J. K. Atwal, S. Steinberg, J. Snaedal, P. V. Jonsson et al., A mutation in APP protects against Alzheimer's disease and age-related cognitive decline, Nature, vol.488, pp.96-99, 2012.

C. D. Kopec, Glutamate Receptor Exocytosis and Spine Enlargement during Chemically Induced Long-Term Potentiation, J. Neurosci, vol.26, 2000.

J. Kril, S. Patel, A. Harding, and G. Halliday, Neuron loss from the hippocampus of Alzheimer's disease exceeds extracellular neurofibrillary tangle formation, Acta Neuropathol. (Berl.), vol.103, pp.370-376, 2002.

T. Krucker, G. R. Siggins, and S. Halpain, Dynamic actin filaments are required for 143, 2000.

, stable long-term potentiation (LTP) in area CA1 of the hippocampus, Proc. Natl. Acad. Sci. U. S. A, vol.97, pp.6856-6861

T. .. Lanz, D. Carter, and K. Merchant, Dendritic spine loss in the hippocampus of young PDAPP and Tg2576 mice and its prevention by the ApoE2 genotype, Neurobiol. Dis, vol.13, pp.246-253, 2003.

A. Matus, M. Ackermann, G. Pehling, H. R. Byers, and K. Fujiwara, High actin concentrations in brain dendritic spines and postsynaptic densities, Proc. Natl. Acad. Sci, vol.79, pp.7590-7594, 1982.

P. Merino-serrais, S. Knafo, L. Alonso-nanclares, I. Fernaud-espinosa, and J. Defelipe, Layer-specific alterations to CA1 dendritic spines in a mouse model of Alzheimer's disease, Hippocampus, vol.21, pp.1037-1044, 2011.

D. L. Moolman, O. V. Vitolo, J. G. Vonsattel, and M. L. Shelanski, Dendrite and dendritic spine alterations in Alzheimer models, J. Neurocytol, vol.33, pp.377-387, 2004.

J. A. Moreno, H. Radford, D. Peretti, J. R. Steinert, N. Verity et al., Sustained translational repression by eIF2?-P mediates prion neurodegeneration, Nature, 2012.

J. Nishiyama, Y. , and R. , Biochemical Computation for Spine Structural Plasticity, Neuron, vol.87, pp.63-75, 2015.

I. Novoa, H. Zeng, H. P. Harding, R. , and D. , Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha, J. Cell Biol, vol.153, pp.1011-1022, 2001.

G. Page, A. Rioux-bilan, S. Ingrand, C. Lafay-chebassier, S. Pain et al., Activated double-stranded RNA-dependent protein kinase and neuronal death in models of Alzheimer's disease, Neuroscience, vol.139, pp.1343-1354, 2006.

A. Peters, S. L. Palay, H. Webster, and . Def, The fine structure of the nervous system: neurons and their supporting cells, 1991.

B. Potier, J. Billard, S. Rivière, P. Sinet, I. Denis et al., Reduction in glutamate uptake is associated with extrasynaptic NMDA and metabotropic glutamate receptor activation at the hippocampal CA1 synapse of aged rats: Synaptic effects of reduced glutamate uptake in the aged rat hippocampus, Aging Cell, vol.9, pp.722-735, 2010.

J. Pozueta, R. Lefort, E. M. Ribe, C. M. Troy, O. Arancio et al., , 2013.

, Caspase-2 is required for dendritic spine and behavioural alterations in J20 APP transgenic mice, Nat. Commun, vol.4

W. Rasband, ImageJ, U.S. National Institutes of Health, 1997.

S. Scheff and P. , Synaptic pathology in Alzheimer's disease: a review of ultrastructural studies, Neurobiol. Aging, vol.24, pp.1029-1046, 2003.

S. W. Scheff, D. A. Price, F. A. Schmitt, S. T. Dekosky, and E. J. Mufson, Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment, Neurology, vol.68, pp.1501-1508, 2007.

D. J. Selkoe, Alzheimer's disease is a synaptic failure, Science, vol.298, pp.789-791, 2002.

D. J. Selkoe and J. Hardy, The amyloid hypothesis of Alzheimer's disease at 25 years, EMBO Mol. Med, vol.8, pp.595-608, 2016.

G. M. Shankar, B. L. Bloodgood, M. Townsend, D. M. Walsh, D. J. Selkoe et al., Natural Oligomers of the Alzheimer Amyloid-Protein Induce Reversible Synapse Loss by Modulating an NMDA-Type Glutamate Receptor-Dependent Signaling Pathway, J. Neurosci, vol.27, pp.2866-2875, 2007.

R. Sherrington, E. I. Rogaev, Y. Liang, E. A. Rogaeva, G. Levesque et al., Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease, Nature, vol.375, pp.754-760, 1995.

T. L. Spires, M. Meyer-luehmann, E. A. Stern, P. J. Mclean, J. Skoch et al., Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy, J. Neurosci. Off. J. Soc. Neurosci, vol.25, pp.7278-7287, 2005.

C. Tackenberg and R. Brandt, Divergent Pathways Mediate Spine Alterations and Cell Death Induced by Amyloid-, Wild-Type Tau, and R406W Tau, J. Neurosci, vol.29, pp.14439-14450, 2009.

R. D. Terry, E. Masliah, D. P. Salmon, N. Butters, R. Deteresa et al., Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment, Ann. Neurol, vol.30, pp.572-580, 1991.

J. Tønnesen and U. V. Nägerl, Dendritic Spines as Tunable Regulators of Synaptic Signals. Front, Psychiatry, vol.7, 2016.

J. Tønnesen, G. Katona, B. Rózsa, and U. V. Nägerl, Spine neck plasticity regulates compartmentalization of synapses, Nat. Neurosci, vol.17, pp.678-685, 2014.

S. Viana-da-silva, M. G. Haberl, P. Zhang, P. Bethge, C. Lemos et al., Early synaptic deficits in the APP/PS1 mouse model of Alzheimer's disease involve neuronal adenosine A2A receptors, Nat. Commun, vol.7, p.11915, 2016.

M. J. West, P. D. Coleman, D. G. Flood, and J. C. Troncoso, Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease, Lancet Lond. Engl, vol.344, pp.769-772, 1994.

J. S. Wiegert and T. G. Oertner, Long-term depression triggers the selective elimination of weakly integrated synapses, Proc. Natl. Acad. Sci, vol.110, pp.4510-4519, 2013.

O. Wirths, H. Breyhan, S. Schäfer, C. Roth, and T. A. Bayer, Deficits in working memory and motor performance in the APP/PS1ki mouse model for Alzheimer's disease, Neurobiol. Aging, vol.29, pp.891-901, 2008.

Q. Zhou, K. J. Homma, and M. Poo, Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses, Neuron, vol.44, pp.749-757, 2004.

C. Zou, E. Montagna, Y. Shi, F. Peters, L. Blazquez-llorca et al., Intraneuronal APP and extracellular A? independently cause dendritic spine pathology in transgenic mouse models of Alzheimer's disease, Acta Neuropathol. (Berl.), vol.129, pp.909-920, 2015.

, Re?fe?rences bibliographiques

J. F. Abisambra, U. K. Jinwal, L. J. Blair, J. C. O'leary, Q. Li et al., Tau Accumulation Activates the Unfolded Protein Response by Impairing Endoplasmic Reticulum-Associated Degradation, J. Neurosci, vol.33, pp.9498-9507, 2013.

W. C. Abraham and J. M. Williams, Properties and Mechanisms of LTP Maintenance, The Neuroscientist, vol.9, pp.463-474, 2003.

Y. Akwa, E. Gondard, A. Mann, E. Capetillo-zarate, E. Alberdi et al., Synaptic activity protects against AD and FTD-like pathology via autophagic-lysosomal degradation, Mol. Psychiatry, 2017.

C. G. Almeida, D. Tampellini, R. H. Takahashi, P. Greengard, M. T. Lin et al., Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses, Neurobiol. Dis, vol.20, pp.187-198, 2005.

V. A. Alvarez and B. L. Sabatini, Anatomical and Physiological Plasticity of Dendritic Spines, Annu. Rev. Neurosci, vol.30, pp.79-97, 2007.

O. M. Andersen, J. Reiche, V. Schmidt, M. Gotthardt, R. Spoelgen et al., Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein, Proc. Natl. Acad. Sci. U. S. A, vol.102, pp.13461-13466, 2005.

R. Araya, J. Jiang, K. B. Eisenthal, and R. Yuste, The spine neck filters membrane potentials, Proc. Natl. Acad. Sci, vol.103, pp.17961-17966, 2006.

T. Arendt, V. Bigl, A. Arendt, and A. Tennstedt, Loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease, paralysis agitans and Korsakoff's Disease, Acta Neuropathol. (Berl.), vol.61, pp.101-108, 1983.

A. Armstrong, N. Mattsson, H. Appelqvist, C. Janefjord, L. Sandin et al., Lysosomal Network Proteins as Potential Novel CSF Biomarkers for Alzheimer's Disease, vol.16, pp.150-160, 2014.

P. V. Arriagada, J. H. Growdon, E. T. Hedley-whyte, and B. T. Hyman, , 1992.

, Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease, Neurology, vol.42, pp.631-639

C. Bancher, I. Grundke-iqbal, K. Iqbal, K. S. Kim, and H. M. Wisniewski, Immunoreactivity of neuronal lipofuscin with monoclonal antibodies to the amyloid betaprotein, Neurobiol. Aging, vol.10, pp.125-132, 1989.

S. Bandyopadhyay, L. E. Goldstein, D. K. Lahiri, and J. T. Rogers, Role of the APP non-amyloidogenic signaling pathway and targeting alpha-secretase as an alternative drug target for treatment of Alzheimer's disease, Curr. Med. Chem, vol.14, pp.2848-2864, 2007.

J. Bär, O. Kobler, B. Van-bommel, and M. Mikhaylova, Periodic F-actin structures shape the neck of dendritic spines, Sci. Rep, vol.6, 2016.

M. F. Bear and R. C. Malenka, Synaptic plasticity: LTP and LTD, Curr. Opin. Neurobiol, vol.4, pp.389-399, 1994.

L. M. Bekris, C. Yu, T. D. Bird, and D. W. Tsuang, Review Article: Genetics of Alzheimer Disease, J. Geriatr. Psychiatry Neurol, vol.23, pp.213-227, 2010.

I. Benilova, E. Karran, D. Strooper, and B. , The toxic A? oligomer and Alzheimer's disease: an emperor in need of clothes, Nat. Neurosci, vol.15, pp.349-357, 2012.

T. A. Benke, A. Lüthi, J. T. Isaac, and G. L. Collingridge, Modulation of AMPA receptor unitary conductance by synaptic activity, Nature, vol.393, pp.793-797, 1998.

S. L. Bernstein, N. F. Dupuis, N. D. Lazo, T. Wyttenbach, M. M. Condron et al., Amyloid-? protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease, Nat. Chem, vol.1, pp.326-331, 2009.

E. Bertling and P. Hotulainen, New waves in dendritic spine actin cytoskeleton: From branches and bundles to rings, from actin binding proteins to post-translational modifications, Mol. Cell. Neurosci, vol.84, pp.77-84, 2017.

A. Bertolotti, Y. Zhang, L. M. Hendershot, H. P. Harding, R. et al., Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response, Nat. Cell Biol, vol.2, p.326, 2000.

L. Bertram, M. B. Mcqueen, K. Mullin, D. Blacker, and R. E. Tanzi, Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database, Nat. Genet, vol.39, pp.17-23, 2007.

L. Bertram, C. M. Lill, and R. E. Tanzi, The Genetics of Alzheimer Disease: Back to the Future, Neuron, vol.68, pp.270-281, 2010.

L. M. Bierer, P. R. Hof, D. P. Purohit, L. Carlin, J. Schmeidler et al., Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer's disease, Arch. Neurol, vol.52, pp.81-88, 1995.

L. M. Billings, S. Oddo, K. N. Green, J. L. Mcgaugh, and F. M. Laferla, , 2005.

, Intraneuronal Abeta causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice, Neuron, vol.45, pp.675-688

T. V. Bliss and G. L. Collingridge, A synaptic model of memory: long-term potentiation in the hippocampus, Nature, vol.361, pp.31-39, 1993.

T. V. Bliss and T. Lomo, Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path, J. Physiol, vol.232, pp.331-356, 1973.

B. L. Bloodgood and B. L. Sabatini, NMDA Receptor-mediated calcium transients in dendritic spines, Biol. NMDA Recept, 2009.

M. Bobinski, J. Wegiel, M. Tarnawski, M. Bobinski, B. Reisberg et al., Relationships between regional neuronal loss and neurofibrillary changes in the hippocampal formation and duration and severity of Alzheimer disease, J. Neuropathol. Exp. Neurol, vol.56, pp.414-420, 1997.

S. Bolognin, E. Lorenzetto, G. Diana, and M. Buffelli, The Potential Role of Rho GTPases in Alzheimer's Disease Pathogenesis, Mol. Neurobiol, vol.50, pp.406-422, 2014.

J. N. Bourne and K. M. Harris, Balancing Structure and Function at Hippocampal Dendritic Spines, Annu. Rev. Neurosci, vol.31, pp.47-67, 2008.

H. Braak and E. Braak, Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections, Brain Pathol. Zurich Switz, vol.1, pp.213-216, 1991.

H. Braak and E. Braak, Neuropathological stageing of Alzheimer-related changes, Acta Neuropathol. (Berl.), vol.82, pp.239-259, 1991.

H. Breyhan, O. Wirths, K. Duan, A. Marcello, J. Rettig et al., , 2009.

, APP/PS1KI bigenic mice develop early synaptic deficits and hippocampus atrophy, Acta Neuropathol. (Berl.), vol.117, pp.677-685

D. I. Briggs, E. Defensor, P. Memar-ardestani, B. Yi, M. Halpain et al., Role of Endoplasmic Reticulum Stress in Learning and Memory Impairment and Alzheimer's Disease-Like Neuropathology in the PS19 and APP Swe Mouse Models of Tauopathy and Amyloidosis, vol.4, pp.25-42, 2017.

J. Brion, H. Passareiro, J. Nunez, and J. Flament-durand, Mise en évidence immunologique de la protéine tau au niveau des lésions de dégénérescence neurofibrillaire de la maladie d'Alzheimer, Arch Biol Brux, vol.95, pp.229-235, 1985.

A. E. Budson and B. H. Price, Memory dysfunction, N. Engl. J. Med, vol.352, pp.692-699, 2005.

L. Buée, T. Bussière, V. Buée-scherrer, A. Delacourte, and P. R. Hof, Tau protein isoforms, phosphorylation and role in neurodegenerative disorders, Brain Res. Brain Res. Rev, vol.33, pp.95-130, 2000.

D. Burdick, B. Soreghan, M. Kwon, J. Kosmoski, M. Knauer et al., Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs, J. Biol. Chem, vol.267, pp.546-554, 1992.

B. Calabrese, G. M. Shaked, I. V. Tabarean, J. Braga, E. H. Koo et al., , 2007.

, Rapid, concurrent alterations in pre-and postsynaptic structure induced by naturally-secreted 182

, Mol. Cell. Neurosci, vol.35, pp.183-193

D. Campion, C. Dumanchin, D. Hannequin, B. Dubois, S. Belliard et al., Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum, Am. J. Hum. Genet, vol.65, pp.664-670, 1999.

G. L. Caporaso, S. E. Gandy, J. D. Buxbaum, and P. Greengard, Chloroquine inhibits intracellular degradation but not secretion of Alzheimer beta/A4 amyloid precursor protein, Proc. Natl. Acad. Sci, vol.89, pp.2252-2256, 1992.

G. L. Caporaso, K. Takei, S. E. Gandy, M. Matteoli, O. Mundigl et al., Morphologic and biochemical analysis of the intracellular trafficking of the Alzheimer beta/A4 amyloid precursor protein, J. Neurosci, vol.14, pp.3122-3138, 1994.

C. Casas, N. Sergeant, J. Itier, V. Blanchard, O. Wirths et al., Massive CA1/2 neuronal loss with intraneuronal and N-terminal truncated Abeta42 accumulation in a novel Alzheimer transgenic model, Am. J. Pathol, vol.165, pp.1289-1300, 2004.

J. M. Castellano, J. Kim, F. R. Stewart, H. Jiang, R. B. Demattos et al., Human apoE Isoforms Differentially Regulate Brain Amyloid-Peptide Clearance, Sci. Transl. Med, vol.3, pp.89-57, 2011.

A. M. Cataldo and R. A. Nixon, Enzymatically active lysosomal proteases are associated with amyloid deposits in Alzheimer brain, Proc. Natl. Acad. Sci. U. S. A, vol.87, pp.3861-3865, 1990.

A. M. Cataldo, J. L. Barnett, D. M. Mann, and R. A. Nixon, Colocalization of lysosomal hydrolase and beta-amyloid in diffuse plaques of the cerebellum and striatum in Alzheimer's disease and Down's syndrome, J. Neuropathol. Exp. Neurol, vol.55, pp.704-715, 1996.

A. M. Cataldo, J. L. Barnett, C. Pieroni, and R. A. Nixon, Increased neuronal endocytosis and protease delivery to early endosomes in sporadic Alzheimer's disease: neuropathologic evidence for a mechanism of increased ?-amyloidogenesis, J. Neurosci, vol.17, pp.6142-6151, 1997.

A. M. Cataldo, C. M. Peterhoff, J. C. Troncoso, T. Gomez-isla, B. T. Hyman et al., Endocytic pathway abnormalities precede amyloid ? deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations, Am. J. Pathol, vol.157, pp.277-286, 2000.

A. M. Cataldo, S. Petanceska, N. B. Terio, C. M. Peterhoff, R. Durham et al., A? localization in abnormal endosomes: association with earliest A? elevations in AD and Down syndrome, Neurobiol. Aging, vol.25, pp.1263-1272, 2004.

S. M. Chafekar, J. J. Hoozemans, R. Zwart, F. Baas, and W. Scheper, , 2007.

, Induces Mild Endoplasmic Reticulum Stress in an Aggregation State-Dependent Manner, Antioxid. Redox Signal, vol.9, pp.2245-2254

E. H. Chang, M. J. Savage, D. G. Flood, J. M. Thomas, R. B. Levy et al., AMPA receptor downscaling at the onset of Alzheimer's disease pathology in double knockin mice, Proc. Natl. Acad. Sci. U. S. A, vol.103, pp.3410-3415, 2006.

R. C. Chang, A. K. Wong, H. Ng, and J. Hugon, Phosphorylation of eukaryotic initiation factor-2? (eIF2?) is associated with neuronal degeneration in Alzheimer's disease, Neuroreport, vol.13, pp.2429-2432, 2002.

R. C. Chang, .. Suen, K. Ma, C. Elyaman, W. Ng et al., Involvement of double-stranded RNA-dependent protein kinase and phosphorylation of eukaryotic initiation factor-2alpha in neuronal degeneration, J. Neurochem, vol.83, pp.1215-1225, 2002.

P. F. Chapman, G. L. White, M. W. Jones, D. Cooper-blacketer, V. J. Marshall et al., Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice, Nat. Neurosci, vol.2, 1999.

S. Chasseigneaux, A. , and B. , Functions of A?, sAPP? and sAPP? : similarities and differences: A? and sAPPs functions, J. Neurochem, vol.120, pp.99-108, 2012.

N. Chaudhari, P. Talwar, A. Parimisetty, C. Lefebvre-d'hellencourt, and P. Ravanan, A Molecular Web: Endoplasmic Reticulum Stress, Inflammation, and Oxidative Stress, Front. Cell. Neurosci, vol.8, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02304218

A. Chazeau and G. Giannone, Organization and dynamics of the actin cytoskeleton during dendritic spine morphological remodeling, Cell. Mol. Life Sci. CMLS, vol.73, pp.3053-3073, 2016.

Y. Chen, J. Bourne, V. A. Pieribone, and R. M. Fitzsimonds, The role of actin in the regulation of dendritic spine morphology and bidirectional synaptic plasticity, Neuroreport, vol.15, pp.829-832, 2004.

S. Choi, D. Kim, T. Kam, S. Yun, S. Kim et al., Lysosomal Enzyme Glucocerebrosidase Protects against A?1-42 Oligomer-Induced Neurotoxicity, vol.10, 2015.

D. Z. Christensen, S. L. Kraus, A. Flohr, M. Cotel, O. Wirths et al., , 2008.

, Transient intraneuronal A? rather than extracellular plaque pathology correlates with neuron loss in the frontal cortex of APP/PS1KI mice, Acta Neuropathol. (Berl.), vol.116, pp.647-655

J. R. Cirrito, K. A. Yamada, M. B. Finn, R. S. Sloviter, K. R. Bales et al., Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo, Neuron, vol.48, pp.913-922, 2005.

M. Citron, D. Westaway, W. Xia, G. Carlson, T. Diehl et al., , p.184

M. Lee, P. Seubert, and A. Davis, Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice, Nat. Med, vol.3, pp.67-72, 1997.

J. P. Cleary, D. M. Walsh, J. J. Hofmeister, G. M. Shankar, M. A. Kuskowski et al., Natural oligomers of the amyloid-? protein specifically disrupt cognitive function, Nat. Neurosci, vol.8, pp.79-84, 2005.

K. Coen, R. S. Flannagan, S. Baron, L. R. Carraro-lacroix, D. Wang et al., Lysosomal calcium homeostasis defects, not proton pump defects, cause endo-lysosomal dysfunction in PSEN-deficient cells, J Cell Biol, vol.198, pp.23-35, 2012.

P. J. Conn and J. Pin, Pharmacology and functions of metabotropic glutamate receptors, Annu. Rev. Pharmacol. Toxicol, vol.37, pp.205-237, 1997.

E. H. Corder, A. M. Saunders, W. J. Strittmatter, D. E. Schmechel, P. C. Gaskell et al., Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families, Science, vol.261, pp.921-923, 1993.

J. Cossec, A. Simon, C. Marquer, R. X. Moldrich, C. Leterrier et al., Clathrin-dependent APP endocytosis and Abeta secretion are highly sensitive to the level of plasma membrane cholesterol, Biochim. Biophys. Acta, vol.1801, pp.846-852, 2010.

M. Costa-mattioli, D. Gobert, E. Stern, K. Gamache, R. Colina et al., eIF2? Phosphorylation Bidirectionally Regulates the Switch from Short-to Long-Term Synaptic Plasticity and Memory, vol.129, pp.195-206, 2007.

J. S. Cox, C. E. Shamu, and P. Walter, Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase, Cell, vol.73, pp.1197-1206, 1993.

P. Cras, M. A. Smith, P. L. Richey, S. L. Siedlak, P. Mulvihill et al., , 1995.

, Extracellular neurofibrillary tangles reflect neuronal loss and provide further evidence of extensive protein cross-linking in Alzheimer disease, Acta Neuropathol. (Berl.), vol.89, pp.291-295

F. C. Crawford, M. J. Freeman, J. A. Schinka, L. I. Abdullah, M. Gold et al., A polymorphism in the cystatin C gene is a novel risk factor for late-onset Alzheimer's disease, Neurology, vol.55, pp.763-768, 2000.

J. L. Cummings, Alzheimer's disease, N. Engl. J. Med, vol.351, pp.56-67, 2004.
URL : https://hal.archives-ouvertes.fr/hal-01579097

C. A. Davies, D. M. Mann, P. Q. Sumpter, and P. O. Yates, A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease, J. Neurol. Sci, vol.78, pp.151-164, 1987.

S. Davis, S. P. Butcher, and R. G. Morris, The NMDA receptor antagonist D-2-amino-5-phosphonopentanoate (D-AP5) impairs spatial learning and LTP in vivo at intracerebral concentrations comparable to those that block LTP in vitro, J. Neurosci, vol.12, pp.21-34, 1992.

C. De-duve, The lysosome turns fifty, Nat. Cell Biol, vol.7, pp.847-849, 2005.

C. De-duve, B. Pressman, R. Gianetto, R. Wattiaux, and F. Appelmans, Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue, Biochem. J, vol.60, p.604, 1955.

B. De-strooper, Proteases and Proteolysis in Alzheimer Disease: A Multifactorial View on the Disease Process, Physiol. Rev, vol.90, pp.465-494, 2010.

B. De-strooper, A. , and W. , Novel Research Horizons for Presenilins and ?-Secretases in Cell Biology and Disease, Annu. Rev. Cell Dev. Biol, vol.26, pp.235-260, 2010.

B. De-strooper, P. Saftig, K. Craessaerts, H. Vanderstichele, G. Guhde et al., Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein, Nature, vol.391, pp.387-390, 1998.

S. T. Dekosky and S. W. Scheff, Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity, Ann. Neurol, vol.27, pp.457-464, 1990.

A. Delacourte and A. Defossez, Alzheimer's disease: Tau proteins, the promoting factors of microtubule assembly, are major components of paired helical filaments, J. Neurol. Sci, vol.76, pp.173-186, 1986.

A. Delacourte, N. Sergeant, A. Wattez, C. Maurage, F. Lebert et al., Tau aggregation in the hippocampal formation: an ageing or a pathological process?, Exp. Gerontol, vol.37, pp.1291-1296, 2002.

P. Delaère, C. Duyckaerts, Y. He, F. Piette, and J. J. Hauw, Subtypes and differential laminar distributions of beta A4 deposits in Alzheimer's disease: relationship with the intellectual status of 26 cases, Acta Neuropathol. (Berl.), vol.81, pp.328-335, 1991.

P. Delaère, Y. He, G. Fayet, C. Duyckaerts, and J. J. Hauw, Beta A4 deposits are constant in the brain of the oldest old: an immunocytochemical study of 20 French centenarians, Neurobiol. Aging, vol.14, pp.191-194, 1993.

E. D'este, D. Kamin, F. Göttfert, A. El-hady, and S. W. Hell, STED Nanoscopy Reveals the Ubiquity of Subcortical Cytoskeleton Periodicity in Living Neurons, Cell Rep, vol.10, pp.1246-1251, 2015.

L. Devi and M. Ohno, PERK mediates eIF2? phosphorylation responsible for BACE1 elevation, CREB dysfunction and neurodegeneration in a mouse model of Alzheimer's disease, Neurobiol. Aging, vol.35, pp.2272-2281, 2014.

I. Dewachter, R. K. Filipkowski, C. Priller, L. Ris, J. Neyton et al., , p.186

M. Gysemans, H. Devijver, and P. Borghgraef, Deregulation of NMDA-receptor function and down-stream signaling in APP[V717I] transgenic mice, Neurobiol. Aging, vol.30, pp.241-256, 2009.

G. V. Di-prisco, W. Huang, S. A. Buffington, C. Hsu, P. E. Bonnen et al., Translational control of mGluR-dependent long-term depression and object-place learning by eIF2?, Nat. Neurosci, vol.17, pp.1073-1082, 2014.

B. C. Dickerson, A. Bakkour, D. H. Salat, E. Feczko, J. Pacheco et al., The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals, Cereb. Cortex, vol.19, pp.497-510, 2009.

J. Dodart, K. R. Bales, K. S. Gannon, S. J. Greene, R. B. Demattos et al., Immunization reverses memory deficits without reducing brain A? burden in Alzheimer's disease model, Nat. Neurosci, 2002.

N. Donnelly, A. M. Gorman, S. Gupta, and A. Samali, The eIF2? kinases: their structures and functions, Cell. Mol. Life Sci, vol.70, pp.3493-3511, 2013.

B. Dubois and K. , Avant la démence, Médecine/Sciences, vol.18, pp.775-779, 2002.

B. Dubois, G. Picard, and M. Sarazin, Early detection of Alzheimer's disease: new diagnostic criteria, Dialogues Clin. Neurosci, vol.11, pp.135-139, 2009.

S. M. Dudek and M. F. Bear, Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade, Proc. Natl. Acad. Sci, vol.89, pp.4363-4367, 1992.

C. Duran-aniotz, V. H. Cornejo, S. Espinoza, Á. O. Ardiles, D. B. Medinas et al., IRE1 signaling exacerbates Alzheimer's disease pathogenesis, Acta Neuropathol. (Berl.), vol.134, pp.489-506, 2017.

C. Duyckaerts, B. Delatour, and M. Potier, Classification and basic pathology of Alzheimer disease, Acta Neuropathol. (Berl.), vol.118, pp.5-36, 2009.

M. Dziembowska and J. Wlodarczyk, MMP9: A novel function in synaptic plasticity, Int. J. Biochem. Cell Biol, vol.44, pp.709-713, 2012.

J. R. Edgar, K. Willen, G. K. Gouras, and C. E. Futter, ESCRTs regulate amyloid precursor protein sorting in multivesicular bodies and intracellular amyloid-accumulation, J. Cell Sci, vol.128, pp.2520-2528, 2015.

C. M. Embury, B. Dyavarshetty, Y. Lu, J. L. Wiederin, P. Ciborowski et al., Cathepsin B Improves ß-Amyloidosis and Learning and Memory, p.187, 2017.

, Models of Alzheimer's Disease, J. Neuroimmune Pharmacol, vol.12, pp.340-352

C. Emiliani, L. Urbanelli, L. Racanicchi, A. Orlacchio, G. Pelicci et al., Up-regulation of Glycohydrolases in Alzheimer's Disease Fibroblasts Correlates with Ras Activation, J. Biol. Chem, vol.278, pp.38453-38460, 2003.

F. Engert and T. Bonhoeffer, Dendritic spine changes associated with hippocampal long-term synaptic plasticity, Nature, vol.399, pp.66-70, 1999.

S. Epelbaum, I. Youssef, P. N. Lacor, P. Chaurand, E. Duplus et al., Acute amnestic encephalopathy in amyloid-? oligomer-injected mice is due to their widespread diffusion in vivo, Neurobiol. Aging, vol.36, pp.2043-2052, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01544165

F. S. Esch, P. S. Keim, E. C. Beattie, R. W. Blacher, A. R. Culwell et al., Cleavage of amyloid ? peptide during constitutive processing of its precursor, pp.1122-1124, 1990.

M. L. Escobar and B. Derrick, Long-Term Potentiation and Depression as Putative Mechanisms for Memory Formation, Neural Plasticity and Memory: From Genes to Brain Imaging, p.p, 2007.

A. Faure, L. Verret, B. Bozon, N. El-tannir-el-tayara, M. Ly et al., Impaired neurogenesis, neuronal loss, and brain functional deficits in the APPxPS1-Ki mouse model of Alzheimer's disease, Neurobiol. Aging, vol.32, pp.407-418, 2011.

S. T. Ferreira and W. L. Klein, The A? oligomer hypothesis for synapse failure and memory loss in Alzheimer's disease, Neurobiol. Learn. Mem, vol.96, pp.529-543, 2011.

J. C. Fiala, J. Spacek, and K. M. Harris, Chapter 1 : Dendrite structure, pp.1-40, 2008.

E. Fifková and R. J. Delay, Cytoplasmic actin in neuronal processes as a possible mediator of synaptic plasticity, J. Cell Biol, vol.95, pp.345-350, 1982.

O. J. Freeman and G. R. Mallucci, The UPR and synaptic dysfunction in neurodegeneration, Brain Res, vol.1648, pp.530-537, 2016.

Y. Fukutani, N. J. Cairns, M. Shiozawa, K. Sasaki, S. Sudo et al., Neuronal loss and neurofibrillary degeneration in the hippocampal cortex in late-onset sporadic Alzheimer's disease, Psychiatry Clin. Neurosci, vol.54, pp.523-529, 2000.

A. Galione, A primer of NAADP-mediated Ca2+ signalling: From sea urchin eggs to mammalian cells, Cell Calcium, vol.58, pp.27-47, 2015.

P. Ghosh, N. M. Dahms, and S. Kornfeld, Mannose 6-phosphate receptors: new twists in the tale, Nat. Rev. Mol. Cell Biol, vol.4, pp.202-213, 2003.

P. Giannakopoulos, F. R. Herrmann, T. Bussiere, C. Bouras, E. Kövari et al., Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease, Neurology, vol.60, pp.1495-1500, 2003.

B. J. Gilbert, The role of amyloid ? in the pathogenesis of Alzheimer's disease, J. Clin. Pathol, vol.66, pp.362-366, 2013.

G. G. Glenner, Amyloid deposits and amyloidosis. The beta-fibrilloses (first of two parts), N. Engl. J. Med, vol.302, pp.1283-1292, 1980.

G. G. Glenner and C. W. Wong, Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein, Biochem. Biophys. Res. Commun, vol.120, pp.885-890, 1984.

A. Goate, M. C. Chartier-harlin, M. Mullan, J. Brown, F. Crawford et al., Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease, Nature, vol.349, pp.704-706, 1991.

M. Goedert, M. G. Spillantini, R. Jakes, D. Rutherford, and R. A. Crowther, , 1989.

, Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease, Neuron, vol.3, pp.519-526

C. A. Gold and A. E. Budson, Memory loss in Alzheimer's disease: implications for development of therapeutics, Expert Rev. Neurother, vol.8, pp.1879-1891, 2008.

T. E. Golde, S. Estus, L. H. Younkin, D. J. Selkoe, and S. G. Younkin, Processing of the amyloid protein precursor to potentially amyloidogenic derivatives, Science, vol.255, pp.728-730, 1992.

D. Goldgaber, M. I. Lerman, O. W. Mcbride, U. Saffiotti, and D. C. Gajdusek, Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease, Science, vol.235, pp.877-880, 1987.

E. D. Goley and M. D. Welch, The ARP2/3 complex: an actin nucleator comes of age, Nat. Rev. Mol. Cell Biol, vol.7, pp.713-726, 2006.

T. Gómez-isla, J. L. Price, D. W. Mckeel, J. C. Morris, J. H. Growdon et al., Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease, J. Neurosci, vol.16, pp.4491-4500, 1996.

T. Gómez-isla, R. Hollister, H. West, S. Mui, J. H. Growdon et al., Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease, Ann. Neurol, vol.41, pp.17-24, 1997.

Y. Gong, L. Chang, K. L. Viola, P. N. Lacor, M. P. Lambert et al., Alzheimer's disease-affected brain: presence of oligomeric A? ligands (ADDLs) suggests a molecular basis for reversible memory loss, Proc. Natl. Acad. Sci, vol.100, pp.10417-10422, 2003.

G. K. Gouras, J. Tsai, J. Naslund, B. Vincent, M. Edgar et al., Intraneuronal Abeta42 accumulation in human brain, Am. J. Pathol, vol.156, pp.15-20, 2000.

E. G. Gray, Axo-somatic and axo-dendritic synapses of the cerebral cortex: an electron microscope study, J. Anat, vol.93, p.420, 1959.

A. Gruart, Involvement of the CA3-CA1 Synapse in the Acquisition of Associative Learning in Behaving Mice, J. Neurosci, vol.26, pp.1077-1087, 2006.

J. Gruenberg and H. Stenmark, The biogenesis of multivesicular endosomes, Nat. Rev. Mol. Cell Biol, vol.5, pp.317-323, 2004.

I. Grundke-iqbal, K. Iqbal, Y. C. Tung, M. Quinlan, H. M. Wisniewski et al., Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology, Proc. Natl. Acad. Sci. U. S. A, vol.83, pp.4913-4917, 1986.

I. Grundke-iqbal, K. Iqbal, M. Quinlan, Y. C. Tung, M. S. Zaidi et al., Microtubule-associated protein tau. A component of Alzheimer paired helical filaments, J. Biol. Chem, vol.261, pp.6084-6089, 1986.

I. Grundke-iqbal, K. Iqbal, L. George, Y. Tung, K. S. Kim et al., Amyloid protein and neurofibrillary tangles coexist in the same neuron in Alzheimer disease, Proc. Natl. Acad. Sci, vol.86, pp.2853-2857, 1989.

K. A. Gyure, R. Durham, W. F. Stewart, J. E. Smialek, and J. C. Troncoso, Intraneuronal abeta-amyloid precedes development of amyloid plaques in Down syndrome, Arch. Pathol. Lab. Med, vol.125, pp.489-492, 2001.

C. Haass and D. J. Selkoe, Cellular processing of ?-amyloid precursor protein and the genesis of amyloid ?-peptide, Cell, vol.75, pp.1039-1042, 1993.

C. Haass, E. H. Koo, A. Mellon, A. Y. Hung, and D. J. Selkoe, Targeting of cellsurface beta-amyloid precursor protein to lysosomes: alternative processing into amyloidbearing fragments, Nature, vol.357, pp.500-503, 1992.

C. Haass, C. A. Lemere, A. Capell, M. Citron, P. Seubert et al., The Swedish mutation causes early-onset Alzheimer's disease by betasecretase cleavage within the secretory pathway, Nat. Med, vol.1, pp.1291-1296, 1995.

C. Haass, C. Kaether, G. Thinakaran, and S. Sisodia, Trafficking and Proteolytic Processing of APP. Cold Spring Harb, Perspect. Med, vol.2, pp.6270-006270, 2012.

G. Halliday, Identifying severely atrophic cortical subregions in Alzheimer's disease, Neurobiol. Aging, vol.24, pp.797-806, 2003.

M. Halliday and G. R. Mallucci, Review: Modulating the unfolded protein response to prevent neurodegeneration and enhance memory: UPR in neurodegeneration and memory, Neuropathol. Appl. Neurobiol, vol.41, pp.414-427, 2015.

M. Halliday, H. Radford, Y. Sekine, J. Moreno, N. Verity et al., Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity, Cell Death Dis, vol.6, p.1672, 2015.

M. Halliday, H. Radford, K. A. Zents, C. Molloy, J. A. Moreno et al., Repurposed drugs targeting eIF2?-Pmediated translational repression prevent neurodegeneration in mice, Brain, vol.140, pp.1768-1783, 2017.

H. P. Harding, Y. Zhang, R. , and D. , Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase, Nature, vol.398, p.90, 1999.

H. P. Harding, I. Novoa, Y. Zhang, H. Zeng, R. Wek et al., Regulated translation initiation controls stress-induced gene expression in mammalian cells, Mol. Cell, vol.6, pp.1099-1108, 2000.

J. Hardy and D. J. Selkoe, The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics, Science, vol.297, pp.353-356, 2002.

J. A. Hardy and G. A. Higgins, Alzheimer's disease: the amyloid cascade hypothesis, Science, vol.256, pp.184-185, 1992.

D. Harold, R. Abraham, P. Hollingworth, R. Sims, A. Gerrish et al., Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease, Nat. Genet, vol.41, pp.1088-1093, 2009.

K. M. Harris and S. B. Kater, Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function, Annu. Rev. Neurosci, vol.17, pp.341-371, 1994.

K. M. Harris and J. K. Stevens, Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics, J. Neurosci, vol.9, pp.2982-2997, 1989.

K. M. Harris, F. E. Jensen, and B. Tsao, Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation, J Neurosci, vol.12, issue.8, 1992.

, J. Neurosci, vol.12, pp.2685-2705

K. Haze, H. Yoshida, H. Yanagi, T. Yura, and K. Mori, Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress, Mol. Biol. Cell, vol.10, pp.3787-3799, 1999.

J. He, R. Zhou, Z. Wu, M. A. Carrasco, P. T. Kurshan et al., Prevalent presence of periodic actin-spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species, Proc. Natl. Acad. Sci. U. S. A, vol.113, pp.6029-6034, 2016.

O. Heinonen, H. Soininen, H. Sorvari, O. Kosunen, L. Paljärvi et al., Loss of synaptophysin-like immunoreactivity in the hippocampal formation is an early phenomenon in Alzheimer's disease, Neuroscience, vol.64, pp.375-384, 1995.

D. A. Henze, J. P. Card, G. Barrionuevo, and Y. Ben-ari, Large amplitude miniature excitatory postsynaptic currents in hippocampal CA3 pyramidal neurons are of mossy fiber origin, J. Neurophysiol, vol.77, pp.1075-1086, 1997.

H. Hering and M. Sheng, Dendritic spines: structure, dynamics and regulation, Nat. Rev. Neurosci, vol.2, pp.880-888, 2001.

B. E. Herring and R. A. Nicoll, Long-Term Potentiation: From CaMKII to AMPA Receptor Trafficking, Annu. Rev. Physiol, vol.78, pp.351-365, 2016.

C. Hetz and S. Saxena, ER stress and the unfolded protein response in neurodegeneration, Nat. Rev. Neurol, vol.13, pp.477-491, 2017.

N. Holderith, A. Lorincz, G. Katona, B. Rózsa, A. Kulik et al., Release probability of hippocampal glutamatergic terminals scales with the size of the active zone, Nat. Neurosci, vol.15, pp.988-997, 2012.

J. J. Hoozemans, R. Veerhuis, E. S. Van-haastert, J. M. Rozemuller, F. Baas et al., The unfolded protein response is activated in Alzheimer's disease, Acta Neuropathol. (Berl.), vol.110, pp.165-172, 2005.

J. J. Hoozemans, E. S. Van-haastert, D. A. Nijholt, A. J. Rozemuller, P. Eikelenboom et al., The Unfolded Protein Response Is Activated in Pretangle Neurons in Alzheimer's Disease Hippocampus, Am. J. Pathol, vol.174, pp.1241-1251, 2009.

P. Hotulainen and C. C. Hoogenraad, Actin in dendritic spines: connecting dynamics to function, J. Cell Biol, vol.189, pp.619-629, 2010.

A. Y. Hsia, E. Masliah, L. Mcconlogue, G. Q. Yu, G. Tatsuno et al., Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models, Proc. Natl. Acad. Sci. U. S. A, vol.96, pp.3228-3233, 1999.

H. Hsieh, J. Boehm, C. Sato, T. Iwatsubo, T. Tomita et al., , 2006.

, AMPAR Removal Underlies A?-Induced Synaptic Depression and Dendritic Spine Loss, Neuron, vol.52, pp.831-843

D. L. Hunt and P. E. Castillo, Synaptic plasticity of NMDA receptors: mechanisms and functional implications, Curr. Opin. Neurobiol, vol.22, pp.496-508, 2012.

M. Hutton, C. L. Lendon, P. Rizzu, M. Baker, S. Froelich et al., Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17, Nature, vol.393, pp.702-705, 1998.

M. Ingelsson, H. Fukumoto, K. L. Newell, J. H. Growdon, E. T. Hedley-whyte et al., , p.192, 2004.

, progressive synaptic loss, gliosis, and tangle formation in AD brain, Neurology, vol.62, pp.925-931

. Inserm, Expertise collective -Maladie d'Alzheimer : Enjeux scientifiques, médicaux et sociétaux, 2007.

K. Iqbal, F. Liu, C. Gong, and I. Grundke-iqbal, Tau in Alzheimer disease and related tauopathies, Curr. Alzheimer Res, vol.7, pp.656-664, 2010.

T. Iwatsubo, A. Odaka, N. Suzuki, H. Mizusawa, N. Nukina et al., , 1994.

, Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43), Neuron, vol.13, pp.45-53

C. R. Jack, R. C. Petersen, Y. Xu, P. C. O'brien, G. E. Smith et al., Rates of hippocampal atrophy correlate with change in clinical status in aging and AD, Neurology, vol.55, pp.484-490, 2000.

J. S. Jacobsen, C. Wu, J. M. Redwine, T. A. Comery, R. Arias et al., Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease, Proc. Natl. Acad. Sci. U. S. A, vol.103, pp.5161-5166, 2006.

R. Jahn and R. H. Scheller, SNAREs--engines for membrane fusion, Nat. Rev. Mol. Cell Biol, vol.7, pp.631-643, 2006.

J. J. Jalbert, L. A. Daiello, and K. L. Lapane, Dementia of the Alzheimer Type, Epidemiol. Rev, vol.30, pp.15-34, 2008.

J. T. Jarrett and P. T. Lansbury, Seeding "one-dimensional crystallization" of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie?, Cell, vol.73, pp.1055-1058, 1993.

S. Jawhar, A. Trawicka, C. Jenneckens, T. A. Bayer, and O. Wirths, Motor deficits, neuron loss, and reduced anxiety coinciding with axonal degeneration and intraneuronal A? aggregation in the 5XFAD mouse model of Alzheimer's disease, Neurobiol. Aging, vol.33, pp.29-40, 0196.

T. Jaworski, S. Kügler, and F. Van-leuven, Modeling of tau-mediated synaptic and neuronal degeneration in Alzheimer's disease, Int. J. Alzheimers Dis, 2010.

L. Jin, F. Shie, I. Maezawa, I. Vincent, and T. Bird, Intracellular accumulation of amyloidogenic fragments of amyloid-beta precursor protein in neurons with Niemann-Pick type C defects is associated with endosomal abnormalities, Am. J. Pathol, vol.164, pp.975-985, 2004.

K. A. Jobst, A. D. Smith, M. Szatmari, A. Molyneux, M. E. Esiri et al., Detection in life of confirmed Alzheimer's disease using a simple measurement of medial temporal lobe atrophy by computed tomography, Lancet Lond. Engl, vol.340, pp.1179-1183, 1992.

E. C. Johnson and J. Kang, A small molecule targeting protein translation does not 193 rescue spatial learning and memory deficits in the hAPP-J20 mouse model of Alzheimer's disease, PeerJ, vol.4, p.2565, 2016.

J. W. Johnson and P. Ascher, Glycine potentiates the NMDA response in cultured mouse brain neurons, Nature, vol.325, pp.529-531, 1987.

T. Jonsson, J. K. Atwal, S. Steinberg, J. Snaedal, P. V. Jonsson et al., A mutation in APP protects against Alzheimer's disease and age-related cognitive decline, Nature, vol.488, pp.96-99, 2012.

K. A. Josephs, J. L. Whitwell, Z. Ahmed, M. M. Shiung, S. D. Weigand et al., ?-amyloid burden is not associated with rates of brain atrophy, Ann. Neurol, vol.63, pp.204-212, 2008.

F. Kamenetz, T. Tomita, H. Hsieh, G. Seabrook, D. Borchelt et al., APP processing and synaptic function, Neuron, vol.37, pp.925-937, 2003.

E. R. Kandel, Nobel Lecture: the molecular biology of memory storage: a dialog between genes and synapses, Biosci. Rep, vol.21, pp.565-611, 2001.

J. Kang, H. G. Lemaire, A. Unterbeck, J. M. Salbaum, C. L. Masters et al., The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor, Nature, vol.325, pp.733-736, 1987.

H. Kasai, M. Matsuzaki, J. Noguchi, N. Yasumatsu, and H. Nakahara, Structurestability-function relationships of dendritic spines, Trends Neurosci, vol.26, pp.360-368, 2003.

J. Kaur and J. Debnath, Autophagy at the crossroads of catabolism and anabolism, Nat. Rev. Mol. Cell Biol, vol.16, pp.461-472, 2015.

G. Kaur, M. Pawlik, S. E. Gandy, M. E. Ehrlich, J. F. Smiley et al., , 2017.

, Lysosomal dysfunction in the brain of a mouse model with intraneuronal accumulation of carboxyl terminal fragments of the amyloid precursor protein, Mol. Psychiatry, vol.22, pp.981-989

C. H. Kim and J. E. Lisman, A role of actin filament in synaptic transmission and long-term potentiation, J. Neurosci. Off. J. Soc. Neurosci, vol.19, pp.4314-4324, 1999.

N. W. Kleckner and R. Dingledine, Requirement for glycine in activation of NMDAreceptors expressed in Xenopus oocytes, Science, vol.241, pp.835-837, 1988.

I. Klyubin, V. Betts, A. T. Welzel, K. Blennow, H. Zetterberg et al., Amyloid Protein Dimer-Containing Human CSF Disrupts Synaptic Plasticity: Prevention by Systemic Passive Immunization, J. Neurosci, vol.28, pp.4231-4237, 2008.

I. Klyubin, W. K. Cullen, N. Hu, and M. J. Rowan, Alzheimer's disease A? assemblies mediating rapid disruption of synaptic plasticity and memory, Mol. Brain, vol.5, p.25, 2012.

A. Kodam, M. Maulik, K. Peake, A. Amritraj, K. S. Vetrivel et al., , p.194

S. Kar, Altered levels and distribution of amyloid precursor protein and its processing enzymes in Niemann-Pick type C1-deficient mouse brains, Glia, vol.58, pp.1267-1281, 2010.

A. Konietzny, J. Bär, and M. Mikhaylova, Dendritic Actin Cytoskeleton: Structure, Functions, and Regulations. Front, Cell. Neurosci, vol.11, 2017.

E. H. Koo and S. L. Squazzo, Evidence that production and release of amyloid betaprotein involves the endocytic pathway, J. Biol. Chem, vol.269, pp.17386-17389, 1994.

E. H. Koo, S. L. Squazzo, D. J. Selkoe, K. , and C. H. , Trafficking of cell-surface amyloid beta-protein precursor. I. Secretion, endocytosis and recycling as detected by labeled monoclonal antibody, J. Cell Sci, vol.109, pp.991-998, 1996.

C. D. Kopec, Glutamate Receptor Exocytosis and Spine Enlargement during Chemically Induced Long-Term Potentiation, J. Neurosci, vol.26, 2000.

E. Korkotian, D. Holcman, and M. Segal, Dynamic regulation of spine-dendrite coupling in cultured hippocampal neurons, Eur. J. Neurosci, vol.20, pp.2649-2663, 2004.

F. Korobova and T. Svitkina, Molecular architecture of synaptic actin cytoskeleton in hippocampal neurons reveals a mechanism of dendritic spine morphogenesis, Mol. Biol. Cell, vol.21, pp.165-176, 2010.

J. Kril, S. Patel, A. Harding, and G. Halliday, Neuron loss from the hippocampus of Alzheimer's disease exceeds extracellular neurofibrillary tangle formation, Acta Neuropathol. (Berl.), vol.103, pp.370-376, 2002.

J. J. Kril, J. Hodges, and G. Halliday, Relationship between hippocampal volume and CA1 neuron loss in brains of humans with and without Alzheimer's disease, Neurosci. Lett, vol.361, pp.9-12, 2004.

T. Krucker, G. R. Siggins, and S. Halpain, Dynamic actin filaments are required for stable long-term potentiation (LTP) in area CA1 of the hippocampus, Proc. Natl. Acad. Sci. U. S. A, vol.97, pp.6856-6861, 2000.

R. Kusters, L. C. Kapitein, C. C. Hoogenraad, and C. Storm, Shape-Induced Asymmetric Diffusion in Dendritic Spines Allows Efficient Synaptic AMPA Receptor Trapping, Biophys. J, vol.105, pp.2743-2750, 2013.

P. N. Lacor, Advances on the understanding of the origins of synaptic pathology in AD, Curr. Genomics, vol.8, pp.486-508, 2007.

P. N. Lacor, M. C. Buniel, P. W. Furlow, A. Sanz-clemente, P. T. Velasco et al., A Oligomer-Induced Aberrations in Synapse Composition, Shape, and Density Provide a Molecular Basis for Loss of Connectivity in Alzheimer's Disease, J. Neurosci, vol.27, pp.796-807, 2007.

F. M. Laferla, K. N. Green, and S. Oddo, Intracellular amyloid-? in Alzheimer's disease, Nat. Rev. Neurosci, vol.8, pp.499-509, 2007.

E. Lai, T. Teodoro, and A. Volchuk, Endoplasmic Reticulum Stress: Signaling the Unfolded Protein Response, Physiology, vol.22, pp.193-201, 2007.

J. Lambert, S. Heath, G. Even, D. Campion, K. Sleegers et al., Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease, Nat. Genet, vol.41, pp.1094-1099, 2009.

C. Lang, A. Barco, L. Zablow, E. R. Kandel, S. A. Siegelbaum et al., Transient expansion of synaptically connected dendritic spines upon induction of hippocampal long-term potentiation, Proc. Natl. Acad. Sci. U. S. A, vol.101, pp.16665-16670, 2004.

D. Langui, N. Girardot, K. H. El-hachimi, B. Allinquant, V. Blanchard et al., Subcellular topography of neuronal A? peptide in APPxPS1 transgenic mice, Am. J. Pathol, vol.165, pp.1465-1477, 2004.

T. .. Lanz, D. Carter, and K. Merchant, Dendritic spine loss in the hippocampus of young PDAPP and Tg2576 mice and its prevention by the ApoE2 genotype, Neurobiol. Dis, vol.13, pp.246-253, 2003.

I. Lauritzen, R. Pardossi-piquard, A. Bourgeois, S. Pagnotta, M. Biferi et al., Intraneuronal aggregation of the ?-CTF fragment of APP (C99) induces A?-independent lysosomal-autophagic pathology, Acta Neuropathol. (Berl.), vol.132, pp.257-276, 2016.

A. Lee, N. N. Iwakoshi, and L. H. Glimcher, XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response, Mol. Cell. Biol, vol.23, pp.7448-7459, 2003.

J. Lee, W. H. Yu, A. Kumar, S. Lee, P. S. Mohan et al., Lysosomal Proteolysis and Autophagy Require Presenilin 1 and Are Disrupted by Alzheimer-Related PS1 Mutations, Cell, vol.141, pp.1146-1158, 2010.

J. Lee, M. K. Mcbrayer, D. M. Wolfe, L. J. Haslett, A. Kumar et al., Presenilin 1 Maintains Lysosomal Ca2+ Homeostasis via TRPML1 by Regulating vATPase-Mediated Lysosome Acidification, Cell Rep, vol.12, pp.1430-1444, 2015.

M. J. De-leon, A. E. George, L. A. Stylopoulos, G. Smith, and D. C. Miller, Early marker for Alzheimer's disease: the atrophic hippocampus, Lancet Lond. Engl, vol.2, pp.672-673, 1989.

J. Lerma and J. M. Marques, Kainate receptors in health and disease, Neuron, vol.80, pp.292-311, 2013.

I. Leshchyns'ka and V. Sytnyk, Reciprocal Interactions between Cell Adhesion Molecules of the Immunoglobulin Superfamily and the Cytoskeleton in Neurons, Front. Cell Dev. Biol, vol.4, p.196, 2016.

S. Lesné, M. T. Koh, L. Kotilinek, R. Kayed, C. G. Glabe et al., A specific amyloid-? protein assembly in the brain impairs memory, Nature, vol.440, pp.352-357, 2006.

A. D. Levy, M. H. Omar, A. J. Koleske, E. Levy-lahad, E. M. Wijsman et al., Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood, Front. Neuroanat, vol.8, pp.970-973, 1995.

E. Levy-lahad, W. Wasco, P. Poorkaj, D. M. Romano, J. Oshima et al., Candidate gene for the chromosome 1 familial Alzheimer's disease locus, Science, vol.269, pp.973-977, 1995.

S. Li, S. Hong, N. E. Shepardson, D. M. Walsh, G. M. Shankar et al., , 2009.

, Soluble Oligomers of Amyloid ? Protein Facilitate Hippocampal Long-Term Depression by Disrupting Neuronal Glutamate Uptake, Neuron, vol.62, pp.788-801

J. Lisman, A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory, Proc. Natl. Acad. Sci, vol.86, pp.9574-9578, 1989.

J. Lisman, R. Yasuda, and S. Raghavachari, Mechanisms of CaMKII action in longterm potentiation, Nat. Rev. Neurosci, 2012.

D. Liu, M. Zhang, Y. , and H. , Signaling Pathways Involved in Endoplasmic Reticulum Stress-Induced Neuronal Apoptosis, Int. J. Neurosci, vol.123, pp.155-162, 2013.

S. Liu, W. Wang, Z. Cai, L. Yao, Z. Chen et al., Polymorphism ?116C/G of Human X-box-Binding Protein 1 Promoter is Associated with Risk of Alzheimer's Disease, CNS Neurosci. Ther, vol.19, pp.229-234, 2013.

M. V. Lourenco, J. R. Clarke, R. L. Frozza, T. R. Bomfim, L. Forny-germano et al., TNF-? Mediates PKR-Dependent Memory Impairment and Brain IRS-1 Inhibition Induced by Alzheimer's ?-Amyloid Oligomers in Mice and Monkeys, Cell Metab, vol.18, pp.831-843, 2013.

L. Lue, Y. Kuo, A. E. Roher, L. Brachova, Y. Shen et al., Soluble amyloid ? peptide concentration as a predictor of synaptic change in Alzheimer's disease, Am. J. Pathol, vol.155, pp.853-862, 1999.

C. Luscher and R. C. Malenka, NMDA Receptor-Dependent Long-Term Potentiation and Long-Term Depression (LTP/LTD), Cold Spring Harb. Perspect. Biol, vol.4, pp.5710-005710, 2012.

J. P. Luzio, M. D. Parkinson, S. R. Gray, and N. A. Bright, The delivery of endocytosed cargo to lysosomes, Biochem. Soc. Trans, vol.37, pp.1019-1021, 2009.

M. A. Lynch, Long-Term Potentiation and Memory, Physiol. Rev, vol.84, pp.87-136, 0197.

Y. Ma and L. M. Hendershot, Delineation of a Negative Feedback Regulatory Loop That Controls Protein Translation during Endoplasmic Reticulum Stress, J. Biol. Chem, vol.278, pp.34864-34873, 2003.

T. Ma, M. A. Trinh, A. J. Wexler, C. Bourbon, E. Gatti et al., Suppression of eIF2? kinases alleviates Alzheimer's disease-related plasticity and memory deficits, Nat. Neurosci, vol.16, pp.1299-1305, 2013.

R. C. Malenka, Synaptic plasticity in the hippocampus: LTP and LTD, Cell, vol.78, pp.535-538, 1994.

R. C. Malenka and R. A. Nicoll, Long-term potentiation-a decade of progress?, Science, vol.285, pp.1870-1874, 1999.

R. Malinow and R. C. Malenka, AMPA Receptor Trafficking and Synaptic Plasticity, Annu. Rev. Neurosci, vol.25, pp.103-126, 2002.

S. J. Marciniak, C. Y. Yun, S. Oyadomari, I. Novoa, Y. Zhang et al., CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum, Genes Dev, vol.18, pp.3066-3077, 2004.

C. Marquer, V. Devauges, J. Cossec, G. Liot, S. Lécart et al., Local cholesterol increase triggers amyloid precursor protein-Bace1 clustering in lipid rafts and rapid endocytosis, FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol, vol.25, pp.1295-1305, 2011.

J. A. Martina, Y. Chen, M. Gucek, and R. Puertollano, MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB, Autophagy, vol.8, pp.903-914, 2012.

E. Masliah, R. D. Terry, R. M. Deteresa, and L. A. Hansen, Immunohistochemical quantification of the synapse-related protein synaptophysin in Alzheimer disease, Neurosci. Lett, vol.103, pp.234-239, 1989.

C. L. Masters, G. Simms, N. A. Weinman, G. Multhaup, B. L. Mcdonald et al., Amyloid plaque core protein in Alzheimer disease and Down syndrome, Proc. Natl. Acad. Sci. U. S. A, vol.82, pp.4245-4249, 1985.

M. Matsuzaki, N. Honkura, G. C. Ellis-davies, and H. Kasai, Structural basis of long-term potentiation in single dendritic spines, Nature, vol.429, pp.761-766, 2004.

A. Matus, M. Ackermann, G. Pehling, H. R. Byers, and K. Fujiwara, High actin concentrations in brain dendritic spines and postsynaptic densities, Proc. Natl. Acad. Sci, vol.79, pp.7590-7594, 1982.

K. G. Mawuenyega, W. Sigurdson, V. Ovod, L. Munsell, T. Kasten et al., Decreased Clearance of CNS -Amyloid in Alzheimer's Disease, Science, vol.330, pp.1774-1774, 2010.

M. L. Mayer, G. L. Westbrook, G. , and P. B. , Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones, Nature, vol.309, pp.261-263, 1984.

R. Mayeux and Y. Stern, Epidemiology of Alzheimer Disease. Cold Spring Harb, Perspect. Med, vol.2, pp.6239-006239, 2012.

K. Mccaffrey and I. Braakman, Protein quality control at the endoplasmic reticulum, Essays Biochem, vol.60, pp.227-235, 2016.

E. Mcglade-mcculloh, H. Yamamoto, S. E. Tan, D. A. Brickey, and T. R. Soderling, Phosphorylation and regulation of glutamate receptors by calcium/calmodulin-dependent protein kinase II, Nature, vol.362, pp.640-642, 1993.

C. A. Mclean, R. A. Cherny, F. W. Fraser, S. J. Fuller, M. J. Smith et al., Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease, Ann. Neurol, vol.46, pp.860-866, 1999.

Y. Meng, Y. Zhang, V. Tregoubov, C. Janus, L. Cruz et al., Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice, Neuron, vol.35, pp.121-133, 2002.

B. Meusser, C. Hirsch, E. Jarosch, and T. Sommer, ERAD: the long road to destruction, Nat. Cell Biol, vol.7, pp.766-772, 2005.

C. A. Miermans, R. P. Kusters, C. C. Hoogenraad, and C. Storm, Biophysical model of the role of actin remodeling on dendritic spine morphology, PloS One, vol.12, 2017.

M. Sanchez, M. Heyn, S. N. Das, D. Moghadam, S. Martin et al., , 2012.

, Neurobiological Elements of Cognitive Dysfunction in Down Syndrome: Exploring the Role of APP, Biol. Psychiatry, vol.71, pp.403-409

M. A. Mintun, G. N. Larossa, Y. I. Sheline, C. S. Dence, S. Y. Lee et al., ). [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease, Neurology, vol.67, pp.446-452, 2006.

N. Mizushima, B. Levine, A. M. Cuervo, and D. J. Klionsky, Autophagy fights disease through cellular self-digestion, Nature, vol.451, pp.1069-1075, 2008.

F. Morena, C. Argentati, R. Trotta, L. Crispoltoni, A. Stabile et al., A Comparison of Lysosomal Enzymes Expression Levels in Peripheral Blood of Mild-and Severe-Alzheimer's Disease and MCI Patients: Implications for Regenerative Medicine Approaches, Int. J. Mol. Sci, vol.18, p.1806, 2017.

J. A. Moreno, H. Radford, D. Peretti, J. R. Steinert, N. Verity et al., Sustained translational repression by eIF2?-P mediates prion neurodegeneration, Nature, 2012.

J. A. Moreno, M. Halliday, C. Molloy, H. Radford, N. Verity et al., , p.199

A. E. Willis, P. M. Fischer, and D. A. Barrett, Oral Treatment Targeting the Unfolded Protein Response Prevents Neurodegeneration and Clinical Disease in Prion-Infected Mice, Sci. Transl. Med, vol.5, pp.206-138, 2013.

R. G. Morris, E. Anderson, G. S. Lynch, and M. Baudry, Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5, Nature, vol.319, pp.774-776, 1986.

L. Mucke, E. Masliah, G. Yu, M. Mallory, E. M. Rockenstein et al., High-level neuronal expression of A?1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation, J. Neurosci, vol.20, pp.4050-4058, 2000.

S. G. Mueller, N. Schuff, K. Yaffe, C. Madison, B. Miller et al., , 2010.

, Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer's disease. Hum, Brain Mapp, vol.31, pp.1339-1347

S. Mueller-steiner, Y. Zhou, H. Arai, E. D. Roberson, B. Sun et al., Antiamyloidogenic and Neuroprotective Functions of Cathepsin B: Implications for Alzheimer's Disease, Neuron, vol.51, pp.703-714, 2006.

R. M. Mulkey and R. C. Malenka, Mechanisms underlying induction of homosynaptic long-term depression in area CA1 of the hippocampus, Neuron, vol.9, pp.967-975, 1992.

R. M. Mulkey, S. Endo, S. Shenolikar, and R. C. Malenka, Involvement of a calcineurin/inhibitor-1 phosphatase cascade in hippocampal long-term depression, Nature, vol.369, pp.486-488, 1994.

U. V. Nägerl, N. Eberhorn, S. B. Cambridge, and T. Bonhoeffer, Bidirectional activity-dependent morphological plasticity in hippocampal neurons, Neuron, vol.44, pp.759-767, 2004.

U. V. Nägerl, K. I. Willig, B. Hein, S. W. Hell, and T. Bonhoeffer, Live-cell imaging of dendritic spines by STED microscopy, Proc. Natl. Acad. Sci. U. S. A, vol.105, pp.18982-18987, 2008.

T. Nakagawa, H. Zhu, N. Morishima, E. Li, J. Xu et al., , 2000.

, Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloidbeta, Nature, vol.403, pp.98-103

J. Näslund, V. Haroutunian, R. Mohs, K. L. Davis, P. Davies et al., Correlation between elevated levels of amyloid ?-peptide in the brain and cognitive decline, Jama, vol.283, pp.1571-1577, 2000.

P. T. Nelson, I. Alafuzoff, E. H. Bigio, C. Bouras, H. Braak et al., Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature, J. Neuropathol. Exp. Neurol, vol.71, pp.362-381, 2012.

C. Nilsberth, A. Westlind-danielsson, C. B. Eckman, M. M. Condron, K. Axelman et al., , p.200

C. Stenh, C. Luthman, J. Teplow, D. B. Younkin, and S. G. , The "Arctic" APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation, Nat. Neurosci, vol.4, pp.887-893, 2001.

E. A. Nimchinsky, B. L. Sabatini, and K. Svoboda, Structure and Function of Dendritic Spines, Annu. Rev. Physiol, vol.64, pp.313-353, 2002.

T. Nishi and M. Forgac, THE VACUOLAR (H+)-ATPASES -NATURE'S MOST VERSATILE PROTON PUMPS, Nat. Rev. Mol. Cell Biol, vol.3, pp.94-103, 2002.

J. Nishiyama, Y. , and R. , Biochemical Computation for Spine Structural Plasticity, Neuron, vol.87, pp.63-75, 2015.

R. A. Nixon, J. Wegiel, A. Kumar, W. H. Yu, C. Peterhoff et al., Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study, J. Neuropathol. Exp. Neurol, vol.64, pp.113-122, 2005.

J. Noguchi, M. Matsuzaki, G. C. Ellis-davies, and H. Kasai, Spine-Neck Geometry Determines NMDA Receptor-Dependent Ca2+ Signaling in Dendrites, Neuron, vol.46, pp.609-622, 2005.

I. Novoa, H. Zeng, H. P. Harding, R. , and D. , Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha, J. Cell Biol, vol.153, pp.1011-1022, 2001.

L. Nowak, P. Bregestovski, P. Ascher, A. Herbet, and A. Prochiantz, Magnesium gates glutamate-activated channels in mouse central neurones, Nature, vol.307, pp.462-465, 1984.

H. Oakley, S. L. Cole, S. Logan, E. Maus, P. Shao et al., Intraneuronal beta-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation, J. Neurosci, vol.26, pp.10129-10140, 2006.

T. O'connor, K. R. Sadleir, E. Maus, R. A. Velliquette, J. Zhao et al., Phosphorylation of the Translation Initiation Factor eIF2? Increases BACE1 Levels and Promotes Amyloidogenesis, Neuron, vol.60, pp.988-1009, 2008.

S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde et al., Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction, Neuron, vol.39, pp.409-421, 2003.

S. Oddo, V. Vasilevko, A. Caccamo, M. Kitazawa, D. H. Cribbs et al., Reduction of Soluble A? and Tau, but Not Soluble A? Alone, Ameliorates Cognitive Decline in Transgenic Mice with Plaques and Tangles, J. Biol. Chem, vol.281, pp.39413-39423, 0201.

S. Oddo, A. Caccamo, I. F. Smith, K. N. Green, and F. M. Laferla, A Dynamic Relationship between Intracellular and Extracellular Pools of A?, Am. J. Pathol, vol.168, pp.184-194, 2006.

S. Ohkuma, Y. Moriyama, and T. Takano, Identification and characterization of a proton pump on lysosomes by fluorescein-isothiocyanate-dextran fluorescence, Proc. Natl. Acad. Sci. U. S. A, vol.79, pp.2758-2762, 1982.

S. Okabe, Molecular anatomy of the postsynaptic density, Mol. Cell. Neurosci, vol.34, pp.503-518, 2007.

K. Okamoto, T. Nagai, A. Miyawaki, and Y. Hayashi, Rapid and persistent modulation of actin dynamics regulates postsynaptic reorganization underlying bidirectional plasticity, Nat. Neurosci, vol.7, pp.1104-1112, 2004.

S. H. Oliet, R. C. Malenka, and R. A. Nicoll, Two distinct forms of long-term depression coexist in CA1 hippocampal pyramidal cells, Neuron, vol.18, pp.969-982, 1997.
URL : https://hal.archives-ouvertes.fr/inserm-00000073

Z. Padamsey, L. Mcguinness, S. J. Bardo, M. Reinhart, R. Tong et al., Activity-Dependent Exocytosis of Lysosomes Regulates the Structural Plasticity of Dendritic Spines, Neuron, vol.93, pp.132-146, 2017.

G. Page, A. Rioux-bilan, S. Ingrand, C. Lafay-chebassier, S. Pain et al., Activated double-stranded RNA-dependent protein kinase and neuronal death in models of Alzheimer's disease, Neuroscience, vol.139, pp.1343-1354, 2006.

K. Pakos-zebrucka, I. Koryga, K. Mnich, M. Ljujic, A. Samali et al., The integrated stress response, EMBO Rep, vol.17, pp.1374-1395, 2016.

M. Palmieri, S. Impey, H. Kang, A. Di-ronza, C. Pelz et al., Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways, Hum. Mol. Genet, vol.20, pp.3852-3866, 2011.

M. Palmieri, R. Pal, H. R. Nelvagal, P. Lotfi, G. R. Stinnett et al., mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases, Nat. Commun, vol.8, 2017.

S. H. Pasternak, R. D. Bagshaw, M. Guiral, S. Zhang, C. A. Ackerley et al., Presenilin-1, nicastrin, amyloid precursor protein, and gamma-secretase activity are co-localized in the lysosomal membrane, J. Biol. Chem, vol.278, pp.26687-26694, 2003.

L. Penazzi, C. Tackenberg, A. Ghori, N. Golovyashkina, B. Niewidok et al., A?-mediated spine changes in the hippocampus are microtubule-dependent and can be reversed by a subnanomolar concentration of the microtubule-stabilizing agent epothilone D, Neuropharmacology, vol.105, p.202, 2016.

A. Peric, A. , and W. , Early etiology of Alzheimer's disease: tipping the balance toward autophagy or endosomal dysfunction?, Acta Neuropathol. (Berl.), vol.129, pp.363-381, 2015.

M. Perluigi, F. Di-domenico, and D. A. Butterfield, mTOR signaling in aging and neurodegeneration: At the crossroad between metabolism dysfunction and impairment of autophagy, Neurobiol. Dis, vol.84, pp.39-49, 2015.

A. Peters, S. L. Palay, H. Webster, and . Def, The fine structure of the nervous system: neurons and their supporting cells, 1991.

F. Pickford, E. Masliah, M. Britschgi, K. Lucin, R. Narasimhan et al., The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid ? accumulation in mice, J. Clin. Invest, 2008.

M. Pitto, F. Raimondo, C. Zoia, L. Brighina, C. Ferrarese et al., , 2005.

, Enhanced GM1 ganglioside catabolism in cultured fibroblasts from Alzheimer patients, Neurobiol. Aging, vol.26, pp.833-838

F. M. Platt, B. Boland, and A. C. Van-der-spoel, Lysosomal storage disorders: The cellular impact of lysosomal dysfunction, J. Cell Biol, vol.199, pp.723-734, 2012.

M. B. Podlisny, B. L. Ostaszewski, S. L. Squazzo, E. H. Koo, R. E. Rydell et al., Aggregation of secreted amyloid beta-protein into sodium dodecyl sulfate-stable oligomers in cell culture, J. Biol. Chem, vol.270, pp.9564-9570, 1995.

V. A. Polito, H. Li, H. Martini-stoica, B. Wang, L. Yang et al., Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB, EMBO Mol. Med, vol.6, pp.1142-1160, 2014.

M. A. Popovic, N. Carnevale, B. Rozsa, and D. Zecevic, Electrical behaviour of dendritic spines as revealed by voltage imaging, Nat. Commun, vol.6, p.8436, 2015.

E. Popugaeva, E. Pchitskaya, A. Speshilova, S. Alexandrov, H. Zhang et al., STIM2 protects hippocampal mushroom spines from amyloid synaptotoxicity, Mol. Neurodegener, vol.10, 2015.

J. Pozueta, R. Lefort, E. M. Ribe, C. M. Troy, O. Arancio et al., , 2013.

, Caspase-2 is required for dendritic spine and behavioural alterations in J20 APP transgenic mice, Nat. Commun, vol.4

J. Pozueta, R. Lefort, and M. L. Shelanski, Synaptic changes in Alzheimer's disease and its models, Neuroscience, vol.251, pp.51-65, 2013.

D. L. Price, R. E. Tanzi, D. R. Borchelt, and S. S. Sisodia, Alzheimer's disease: genetic studies and transgenic models, Annu. Rev. Genet, vol.32, pp.461-493, 1998.

P. and J. , Alzheimer's Disease International), World Alzheimer Report, 2009.

M. Prince, R. Bryce, E. Albanese, A. Wimo, W. Ribeiro et al., The global prevalence of dementia: a systematic review and metaanalysis, Alzheimers Dement. J. Alzheimers Assoc, vol.9, pp.63-75, 2013.

D. Purves, A. Augustine, D. Fitzpatrick, W. Hall, A. Lamantia et al., Neuroscience, 2004.

H. W. Querfurth and F. M. Laferla, Alzheimer's disease, N. Engl. J. Med, vol.362, pp.329-344, 2010.

H. Radford, J. A. Moreno, N. Verity, M. Halliday, and G. R. Mallucci, PERK inhibition prevents tau-mediated neurodegeneration in a mouse model of frontotemporal dementia, Acta Neuropathol. (Berl.), vol.130, pp.633-642, 2015.

L. Rajendran, A. , and W. , Membrane Trafficking Pathways in Alzheimer's Disease: Membrane Trafficking and Alzheimer's Disease, Traffic, vol.13, pp.759-770, 2012.

L. Rajendran, M. Honsho, T. R. Zahn, P. Keller, K. D. Geiger et al.,

, Alzheimer's disease beta-amyloid peptides are released in association with exosomes, Proc. Natl. Acad. Sci. U. S. A, vol.103, pp.11172-11177

B. Ramachandran and J. U. Frey, Interfering with the Actin Network and Its Effect on Long-Term Potentiation and Synaptic Tagging in Hippocampal CA1 Neurons in Slices In Vitro, J. Neurosci, vol.29, pp.12167-12173, 2009.

A. Roczniak-ferguson, C. S. Petit, F. Froehlich, S. Qian, J. Ky et al., The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis, Sci. Signal, vol.5, p.42, 2012.

D. Ron and P. Walter, Signal integration in the endoplasmic reticulum unfolded protein response, Nat. Rev. Mol. Cell Biol, vol.8, pp.519-529, 2007.

F. Roselli, Soluble -Amyloid1-40 Induces NMDA-Dependent Degradation of Postsynaptic Density-95 at Glutamatergic Synapses, J. Neurosci, vol.25, pp.11061-11070, 2005.

A. Rovelet-lecrux, D. Hannequin, G. Raux, N. L. Meur, A. Laquerrière et al., APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy, Nat. Genet, vol.38, pp.24-26, 2006.

D. T. Rutkowski and R. J. Kaufman, A trip to the ER: coping with stress, Trends Cell Biol, vol.14, pp.20-28, 2004.

B. P. Rutten, N. M. Van-der-kolk, S. Schafer, M. A. Van-zandvoort, T. A. Bayer et al., Age-Related Loss of Synaptophysin Immunoreactive 204, 2005.

, Presynaptic Boutons within the Hippocampus of APP751 SL, PS1 M146L, and APP751 SL/PS1 M146L Transgenic Mice, Am. J. Pathol, vol.167, pp.161-173

J. Ryu, L. Liu, T. P. Wong, D. C. Wu, A. Burette et al., A Critical Role for Myosin IIB in Dendritic Spine Morphology and Synaptic Function, Neuron, vol.49, pp.175-182, 2006.

P. Saftig and J. Klumperman, Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function, Nat. Rev. Mol. Cell Biol, vol.10, pp.623-635, 2009.

R. Sannerud, C. Esselens, P. Ejsmont, R. Mattera, L. Rochin et al., Restricted Location of PSEN2/?-Secretase Determines Substrate Specificity and Generates an Intracellular A? Pool, Cell, vol.166, pp.193-208, 2016.

M. Sardiello, M. Palmieri, A. Di-ronza, D. L. Medina, M. Valenza et al., A gene network regulating lysosomal biogenesis and function, Science, vol.325, pp.473-477, 2009.

S. Sarkar, J. E. Davies, Z. Huang, A. Tunnacliffe, and D. C. Rubinsztein, Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein, J. Biol. Chem, vol.282, pp.5641-5652, 2007.

V. Schaeffer, I. Lavenir, S. Ozcelik, M. Tolnay, D. T. Winkler et al., Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy, Brain, vol.135, pp.2169-2177, 2012.

S. Scheff, Synaptic pathology in Alzheimer's disease: a review of ultrastructural studies, Neurobiol. Aging, vol.24, pp.1029-1046, 2003.

S. W. Scheff and D. A. Price, Synapse loss in the temporal lobe in Alzheimer's disease, Ann. Neurol, vol.33, pp.190-199, 1993.

S. W. Scheff, S. T. Dekosky, and D. A. Price, Quantitative assessment of cortical synaptic density in Alzheimer's disease, Neurobiol. Aging, vol.11, pp.29-37, 1990.

S. W. Scheff, L. Sparks, and D. A. Price, Quantitative assessment of synaptic density in the entorhinal cortex in Alzheimer's disease, Ann. Neurol, vol.34, pp.356-361, 1993.

S. W. Scheff, D. A. Price, F. A. Schmitt, and E. J. Mufson, Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment, Neurobiol. Aging, vol.27, pp.1372-1384, 2006.

S. W. Scheff, D. A. Price, F. A. Schmitt, S. T. Dekosky, and E. J. Mufson, Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment, Neurology, vol.68, pp.1501-1508, 2007.

W. Scheper and J. J. Hoozemans, The unfolded protein response in neurodegenerative diseases: a neuropathological perspective, Acta Neuropathol. (Berl.), vol.130, p.205, 2015.

D. Scheuner, C. Eckman, M. Jensen, X. Song, M. Citron et al., Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease, Nat. Med, vol.2, pp.864-870, 1996.

T. Schikorski and C. F. Stevens, Morphological correlates of functionally defined synaptic vesicle populations, Nat. Neurosci, vol.4, pp.391-395, 2001.

R. Schliebs, A. , and T. , The cholinergic system in aging and neuronal degeneration, Behav. Brain Res, vol.221, pp.555-563, 2011.

C. Schmitz, B. P. Rutten, A. Pielen, S. Schäfer, O. Wirths et al., Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer's disease, Am. J. Pathol, vol.164, pp.1495-1502, 2004.

M. L. Schultz, L. Tecedor, M. Chang, and B. L. Davidson, Clarifying lysosomal storage diseases, Trends Neurosci, vol.34, pp.401-410, 2011.

S. S. Sekhon and D. S. Maxwell, Ultrastructural changes in neurons of the spinal anterior horn of ageing mice with particular reference to the accumulation of lipofuscin pigment, J. Neurocytol, vol.3, pp.59-72, 1974.

D. J. Selkoe, Soluble oligomers of the amyloid ?-protein impair synaptic plasticity and behavior, Behav. Brain Res, vol.192, pp.106-113, 2008.

D. J. Selkoe and J. Hardy, The amyloid hypothesis of Alzheimer's disease at 25 years, EMBO Mol. Med, vol.8, pp.595-608, 2016.

A. Serrano-pozo, M. P. Frosch, E. Masliah, and B. T. Hyman, Neuropathological Alterations in Alzheimer Disease, Cold Spring Harb. Perspect. Med, vol.1, pp.6189-006189, 2011.

S. Seshadri, A. L. Fitzpatrick, M. A. Ikram, A. L. Destefano, V. Gudnason et al., Genome-wide analysis of genetic loci associated with Alzheimer disease, JAMA, vol.303, pp.1832-1840, 2010.

C. Settembre, C. Di-malta, V. A. Polito, M. Garcia-arencibia, F. Vetrini et al., TFEB links autophagy to lysosomal biogenesis, vol.332, pp.1429-1433, 2011.

C. Settembre, R. Zoncu, D. L. Medina, F. Vetrini, S. Erdin et al., A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB, EMBO J, vol.31, pp.1095-1108, 2012.

C. Settembre, A. Fraldi, D. L. Medina, and A. Ballabio, Signals from the lysosome: a control centre for cellular clearance and energy metabolism, Nat. Rev. Mol. Cell Biol, vol.14, pp.283-296, 2013.

C. E. Shamu and P. Walter, Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus, EMBO J, vol.15, pp.3028-3039, 1996.

G. M. Shankar, B. L. Bloodgood, M. Townsend, D. M. Walsh, D. J. Selkoe et al., Natural Oligomers of the Alzheimer Amyloid-Protein Induce Reversible Synapse Loss by Modulating an NMDA-Type Glutamate Receptor-Dependent Signaling Pathway, J. Neurosci, vol.27, pp.2866-2875, 2007.

G. M. Shankar, S. Li, T. H. Mehta, A. Garcia-munoz, N. E. Shepardson et al., Amyloid-? protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory, Nat. Med, vol.14, pp.837-842, 2008.

H. Shen and N. Mizushima, At the end of the autophagic road: an emerging understanding of lysosomal functions in autophagy, Trends Biochem. Sci, vol.39, pp.61-71, 2014.

R. Sherrington, E. I. Rogaev, Y. Liang, E. A. Rogaeva, G. Levesque et al., Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease, Nature, vol.375, pp.754-760, 1995.

G. C. Shore, F. R. Papa, and S. A. Oakes, Signaling cell death from the endoplasmic reticulum stress response, Curr. Opin. Cell Biol, vol.23, pp.143-149, 2011.

B. R. Shrestha, O. V. Vitolo, P. Joshi, T. Lordkipanidze, M. Shelanski et al., Amyloid ? peptide adversely affects spine number and motility in hippocampal neurons, Mol. Cell. Neurosci, vol.33, pp.274-282, 2006.

S. C. Sidenstein, E. D'este, M. J. Böhm, J. G. Danzl, V. N. Belov et al., , 2016.

, Multicolour Multilevel STED nanoscopy of Actin/Spectrin Organization at Synapses. Sci. Rep, vol.6, p.26725

C. Sidrauski and P. Walter, The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response, Cell, vol.90, pp.1031-1039, 1997.

C. Sidrauski, D. Acosta-alvear, A. Khoutorsky, P. Vedantham, B. R. Hearn et al., Pharmacological brakerelease of mRNA translation enhances cognitive memory, vol.2, p.498, 2013.

C. Sidrauski, J. C. Tsai, M. Kampmann, B. R. Hearn, P. Vedantham et al., Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response, vol.4, p.7314, 2015.

C. Sidrauski, A. M. Mcgeachy, N. T. Ingolia, and P. Walter, The small molecule ISRIB reverses the effects of eIF2? phosphorylation on translation and stress granule assembly, vol.4, p.5033, 2015.

R. Siman, R. Cocca, D. , and Y. , The mTOR Inhibitor Rapamycin Mitigates Perforant Pathway Neurodegeneration and Synapse Loss in a Mouse Model of Early-Stage Alzheimer-Type Tauopathy, PLOS ONE, vol.10, 2015.

G. Simi?, I. Kostovi?, B. Winblad, and N. Bogdanovi?, Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer's disease, J. Comp. Neurol, vol.379, pp.482-494, 1997.

S. Sinha, J. P. Anderson, R. Barbour, G. S. Basi, R. Caccavello et al., Purification and cloning of amyloid precursor protein beta-secretase from human brain, Nature, vol.402, pp.537-540, 1999.

S. S. Sisodia, Beta-amyloid precursor protein cleavage by a membrane-bound protease, Proc. Natl. Acad. Sci. U. S. A, vol.89, pp.6075-6079, 1992.

S. S. Sisodia, E. H. Koo, K. Beyreuther, A. Unterbeck, and D. L. Price, Evidence that beta-amyloid protein in Alzheimer's disease is not derived by normal processing, Science, vol.248, pp.492-495, 1990.

R. Sitia and I. Braakman, Quality control in the endoplasmic reticulum protein factory, Nature, vol.426, pp.891-894, 2003.

D. E. Sleat, M. Jadot, and P. Lobel, Lysosomal proteomics and disease, PROTEOMICS -Clin. Appl, vol.1, pp.1134-1146, 2007.

M. H. Smith, H. L. Ploegh, and J. S. Weissman, Road to ruin: targeting proteins for degradation in the endoplasmic reticulum, Science, vol.334, pp.1086-1090, 2011.

E. M. Snyder, Y. Nong, C. G. Almeida, S. Paul, T. Moran et al., Regulation of NMDA receptor trafficking by amyloid-?, Nat. Neurosci, vol.8, pp.1051-1058, 2005.

A. Sobczyk, NMDA Receptor Subunit-Dependent [Ca2+] Signaling in Individual Hippocampal Dendritic Spines, J. Neurosci, vol.25, pp.6037-6046, 2005.

S. Soriano, A. S. Chyung, X. Chen, G. B. Stokin, V. M. Lee et al., Expression of beta-amyloid precursor protein-CD3gamma chimeras to demonstrate the selective generation of amyloid beta(1-40) and amyloid beta(1-42) peptides within secretory and endocytic compartments, J. Biol. Chem, vol.274, pp.32295-32300, 1999.

P. Spilman, N. Podlutskaya, M. J. Hart, J. Debnath, O. Gorostiza et al., Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-? Levels in a Mouse Model of Alzheimer's Disease, PLoS ONE, vol.5, p.9979, 2010.

T. L. Spires, M. Meyer-luehmann, E. A. Stern, P. J. Mclean, J. Skoch et al., Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy, p.208, 2005.

, J. Neurosci, vol.25, pp.7278-7287

L. R. Squire, F. E. Bloom, N. C. Spitzer, S. Du-lac, A. Ghosh et al., , 2008.

, Fundamental neuroscience

S. George-hyslop, P. Haines, J. Rogaev, E. Mortilla, M. Vaula et al., Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14, Nat. Genet, vol.2, pp.330-334, 1992.

W. J. Strittmatter, A. M. Saunders, D. Schmechel, M. Pericak-vance, J. Enghild et al., Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease, Proc. Natl. Acad. Sci. U. S. A, vol.90, pp.1977-1981, 1993.

L. D. Stutzbach, S. X. Xie, A. C. Naj, R. Albin, S. Gilman et al., The unfolded protein response is activated in disease-affected brain regions in progressive supranuclear palsy and Alzheimer's disease, Acta Neuropathol. Commun, vol.1, p.31, 2013.

K. Suen, M. Yu, K. So, R. Chang, and J. Hugon, Upstream Signaling Pathways Leading to the Activation of Double-stranded RNA-dependent Serine/Threonine Protein Kinase in ?-Amyloid Peptide Neurotoxicity, J. Biol. Chem, vol.278, pp.49819-49827, 2003.

B. Sun, Y. Zhou, B. Halabisky, I. Lo, S. Cho et al., Cystatin C-Cathepsin B Axis Regulates Amyloid Beta Levels and Associated Neuronal Deficits in an Animal Model of Alzheimer's Disease, Neuron, vol.60, pp.247-257, 2008.

C. I. Sze, J. C. Troncoso, C. Kawas, P. Mouton, D. L. Price et al., Loss of the presynaptic vesicle protein synaptophysin in hippocampus correlates with cognitive decline in Alzheimer disease, J. Neuropathol. Exp. Neurol, vol.56, pp.933-944, 1997.

E. Szegezdi, S. E. Logue, A. M. Gorman, and A. Samali, Mediators of endoplasmic reticulum stress-induced apoptosis, EMBO Rep, vol.7, pp.880-885, 2006.

I. Tabas, R. , and D. , Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress, Nat. Cell Biol, vol.13, pp.184-190, 2011.

C. Tackenberg and R. Brandt, Divergent Pathways Mediate Spine Alterations and Cell Death Induced by Amyloid-, Wild-Type Tau, and R406W Tau, J. Neurosci, vol.29, pp.14439-14450, 2009.

R. H. Takahashi, T. A. Milner, F. Li, E. E. Nam, M. A. Edgar et al., Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology, Am. J. Pathol, vol.161, pp.1869-1879, 2002.

R. H. Takahashi, T. Nagao, and G. K. Gouras, Plaque formation and the intraneuronal 209 accumulation of ?-amyloid in Alzheimer's disease: Intraneuronal accumulation of ?-amyloid, Pathol. Int, vol.67, pp.185-193, 2017.

K. Takasaki and B. L. Sabatini, Super-resolution 2-photon microscopy reveals that the morphology of each dendritic spine correlates with diffusive but not synaptic properties, Front. Neuroanat, vol.8, 2014.

N. Takasugi, T. Tomita, I. Hayashi, M. Tsuruoka, M. Niimura et al., The role of presenilin cofactors in the gamma-secretase complex, Nature, vol.422, pp.438-441, 2003.

Y. Takumi, V. Ramírez-león, P. Laake, E. Rinvik, and O. P. Ottersen, Different modes of expression of AMPA and NMDA receptors in hippocampal synapses, Nat. Neurosci, vol.2, pp.618-624, 1999.

P. Tammineni, Y. Y. Jeong, T. Feng, D. Aikal, and Q. Cai, Impaired axonal retrograde trafficking of the retromer complex augments lysosomal deficits in Alzheimer's disease neurons, Hum. Mol. Genet, 2017.

D. Tampellini, N. Rahman, E. F. Gallo, Z. Huang, M. Dumont et al., Synaptic activity reduces intraneuronal Abeta, promotes APP transport to synapses, and protects against Abeta-related synaptic alterations, J. Neurosci. Off. J. Soc. Neurosci, vol.29, pp.9704-9713, 2009.

D. Tampellini, E. Capetillo-zarate, M. Dumont, Z. Huang, F. Yu et al., Effects of synaptic modulation on beta-amyloid, synaptophysin, and memory performance in Alzheimer's disease transgenic mice, J. Neurosci. Off. J. Soc. Neurosci, vol.30, pp.14299-14304, 2010.

R. E. Tanzi, The Genetics of Alzheimer Disease. Cold Spring Harb, Perspect. Med, vol.2, pp.6296-006296, 2012.

R. E. Tanzi, J. F. Gusella, P. C. Watkins, G. A. Bruns, P. St-george-hyslop et al., Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus, Science, vol.235, pp.880-884, 1987.

R. Tarawneh and D. M. Holtzman, The clinical problem of symptomatic Alzheimer disease and mild cognitive impairment. Cold Spring Harb, Perspect. Med, vol.2, p.6148, 2012.

R. D. Terry, E. Masliah, D. P. Salmon, N. Butters, R. Deteresa et al., Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment, Ann. Neurol, vol.30, pp.572-580, 1991.

D. R. Thal, U. Rüb, M. Orantes, and H. Braak, Phases of A beta-deposition in the human brain and its relevance for the development of AD, Neurology, vol.58, pp.1791-1800, 2002.

C. C. Thoreen and D. M. Sabatini, Rapamycin inhibits mTORC1, but not completely, p.210, 2009.

, Autophagy, vol.5, pp.725-726

C. C. Thoreen, S. A. Kang, J. W. Chang, Q. Liu, J. Zhang et al., An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1, J. Biol. Chem, vol.284, pp.8023-8032, 2009.

H. Togashi, T. Sakisaka, and Y. Takai, Cell adhesion molecules in the central nervous system, Cell Adhes. Migr, vol.3, pp.29-35, 2009.

J. Tønnesen and U. V. Nägerl, Dendritic Spines as Tunable Regulators of Synaptic Signals. Front, Psychiatry, vol.7, 2016.

J. Tønnesen, G. Katona, B. Rózsa, and U. V. Nägerl, Spine neck plasticity regulates compartmentalization of synapses, Nat. Neurosci, vol.17, pp.678-685, 2014.

M. Torres, S. Jimenez, R. Sanchez-varo, V. Navarro, L. Trujillo-estrada et al., Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus, Mol. Neurodegener, vol.7, p.59, 2012.

M. Townsend, G. M. Shankar, T. Mehta, D. M. Walsh, and D. J. Selkoe, Effects of secreted oligomers of amyloid ?-protein on hippocampal synaptic plasticity: a potent role for trimers: Amyloid ?-protein and hippocampal synaptic plasticity, J. Physiol, vol.572, pp.477-492, 2006.

S. F. Traynelis, L. P. Wollmuth, C. J. Mcbain, F. S. Menniti, K. M. Vance et al., Glutamate Receptor Ion Channels: Structure, Regulation, and Function, Pharmacol. Rev, vol.62, pp.405-496, 2010.

M. A. Trinh, T. Ma, H. Kaphzan, A. Bhattacharya, M. D. Antion et al., The eIF2 kinase PERK limits the expression of hippocampal metabotropic glutamate receptor-dependent long-term depression, Learn. Mem, vol.21, pp.298-304, 2014.

J. Q. Trojanowski and V. M. Lee, Phosphorylation of paired helical filament tau in Alzheimer's disease neurofibrillary lesions: focusing on phosphatases, FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol, vol.9, pp.1570-1576, 1995.

U. Unterberger, R. Höftberger, E. Gelpi, H. Flicker, H. Budka et al., , 2006.

, Endoplasmic reticulum stress features are prominent in Alzheimer disease but not in prion diseases in vivo, J. Neuropathol. Exp. Neurol, vol.65, pp.348-357

F. Urano, X. Wang, A. Bertolotti, Y. Zhang, P. Chung et al., Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1, Science, vol.287, pp.664-666, 2000.

L. Urbanelli, C. Emiliani, C. Massini, E. Persichetti, A. Orlacchio et al., Cathepsin D expression is, p.211, 2008.

, Alzheimer's disease fibroblasts, Neurobiol. Aging, vol.29, pp.12-22

R. Vassar, B. D. Bennett, S. Babu-khan, S. Kahn, E. A. Mendiaz et al., Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE, Science, vol.286, pp.735-741, 1999.

T. H. Vereecken, O. J. Vogels, and R. Nieuwenhuys, Neuron loss and shrinkage in the amygdala in Alzheimer's disease, Neurobiol. Aging, vol.15, pp.45-54, 1994.

D. M. Walsh, Certain Inhibitors of Synthetic Amyloid -Peptide (A ) Fibrillogenesis Block Oligomerization of Natural A and Thereby Rescue Long-Term Potentiation, J. Neurosci, vol.25, pp.2455-2462, 2005.

D. M. Walsh, B. P. Tseng, R. E. Rydel, M. B. Podlisny, and D. J. Selkoe, The Oligomerization of Amyloid ?-Protein Begins Intracellularly in Cells Derived from Human Brain ?, Biochemistry (Mosc.), vol.39, pp.10831-10839, 2000.

D. M. Walsh, I. Klyubin, J. V. Fadeeva, W. K. Cullen, R. Anwyl et al., Naturally secreted oligomers of amyloid ? protein potently inhibit hippocampal long-term potentiation in vivo, Nature, vol.416, pp.535-539, 2002.

D. M. Walsh, I. Klyubin, J. V. Fadeeva, M. J. Rowan, and D. J. Selkoe, Amyloid-? oligomers: their production, toxicity and therapeutic inhibition, 2002.

P. Walter, R. , and D. , The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation, Science, vol.334, pp.1081-1086, 2011.

M. Wang and R. J. Kaufman, Protein misfolding in the endoplasmic reticulum as a conduit to human disease, Nature, vol.529, pp.326-335, 2016.

H. Wang, J. F. Pasternak, H. Kuo, H. Ristic, M. P. Lambert et al., Soluble oligomers of ? amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus, Brain Res, vol.924, pp.133-140, 2002.

X. Wang, O. Bozdagi, J. S. Nikitczuk, Z. W. Zhai, Q. Zhou et al., , 2008.

, Extracellular proteolysis by matrix metalloproteinase-9 drives dendritic spine enlargement and long-term potentiation coordinately, Proc. Natl. Acad. Sci. 105, pp.19520-19525

X. Wang, X. Zhou, G. Li, Y. Zhang, Y. Wu et al., Modifications and Trafficking of APP in the Pathogenesis of Alzheimer's Disease, Front. Mol. Neurosci, vol.10, 2017.

M. J. West, P. D. Coleman, D. G. Flood, and J. C. Troncoso, Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease, Lancet Lond. Engl, vol.344, pp.769-772, 1994.

P. J. Whitehouse, D. L. Price, A. W. Clark, J. T. Coyle, and M. R. Delong, Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis, Ann. Neurol, vol.212, pp.122-126, 1981.

J. R. Whitlock, A. J. Heynen, M. G. Shuler, and M. F. Bear, Learning induces longterm potentiation in the hippocampus, Science, vol.313, pp.1093-1097, 2006.

J. L. Whitwell, Progression of Atrophy in Alzheimer's Disease and Related Disorders, Neurotox. Res, vol.18, pp.339-346, 2010.

J. L. Whitwell, K. A. Josephs, M. E. Murray, K. Kantarci, S. A. Przybelski et al., MRI correlates of neurofibrillary tangle pathology at autopsy A voxel-based morphometry study, Neurology, vol.71, pp.743-749, 2008.

L. S. Whyte, A. A. Lau, K. M. Hemsley, J. J. Hopwood, and T. J. Sargeant, Endolysosomal and autophagic dysfunction: a driving factor in Alzheimer's disease?, J. Neurochem, vol.140, pp.703-717, 2017.

J. S. Wiegert and T. G. Oertner, Long-term depression triggers the selective elimination of weakly integrated synapses, Proc. Natl. Acad. Sci, vol.110, pp.4510-4519, 2013.

K. C. Wilcox, P. N. Lacor, J. Pitt, and W. L. Klein, A? Oligomer-Induced Synapse Degeneration in Alzheimer's Disease, Cell. Mol. Neurobiol, vol.31, pp.939-948, 2011.

P. Wimo, The global economic impact of dementia (Alzheimer's Disease International), 2010.

O. Wirths and T. A. Bayer, Neuron Loss in Transgenic Mouse Models of Alzheimer's Disease, Int. J. Alzheimers Dis, vol.2010, pp.1-6, 2010.

O. Wirths and T. A. Bayer, Intraneuronal A? accumulation and neurodegeneration: lessons from transgenic models, Life Sci, vol.91, pp.1148-1152, 2012.

O. Wirths, G. Multhaup, C. Czech, V. Blanchard, S. Moussaoui et al., Intraneuronal Abeta accumulation precedes plaque formation in beta-amyloid precursor protein and presenilin-1 double-transgenic mice, Neurosci. Lett, vol.306, pp.116-120, 2001.

O. Wirths, G. Multhaup, C. Czech, N. Feldmann, V. Blanchard et al., Intraneuronal APP/A beta trafficking and plaque formation in beta-amyloid precursor protein and presenilin-1 transgenic mice, Brain Pathol. Zurich Switz, vol.12, pp.275-286, 2002.

O. Wirths, G. Multhaup, and T. A. Bayer, A modified beta-amyloid hypothesis: intraneuronal accumulation of the beta-amyloid peptide--the first step of a fatal cascade, J. Neurochem, vol.91, pp.513-520, 2004.

K. E. Wisniewski, H. M. Wisniewski, and G. Y. Wen, Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome, Ann. Neurol, vol.17, pp.278-282, 1985.

Q. Xiao, P. Yan, X. Ma, H. Liu, R. Perez et al., Neuronal-Targeted TFEB Accelerates Lysosomal Degradation of APP, Reducing A Generation and Amyloid Plaque Pathogenesis, J. Neurosci, vol.35, pp.12137-12151, 2015.

K. Xu, G. Zhong, and X. Zhuang, Actin, Spectrin, and Associated Proteins Form a Periodic Cytoskeletal Structure in Axons, Science, vol.339, pp.452-456, 2013.

K. Yamamoto, T. Sato, T. Matsui, M. Sato, T. Okada et al., Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1, Dev. Cell, vol.13, pp.365-376, 2007.

T. Yamazaki, E. H. Koo, and D. J. Selkoe, Trafficking of cell-surface amyloid betaprotein precursor. II. Endocytosis, recycling and lysosomal targeting detected by immunolocalization, J. Cell Sci, vol.109, pp.999-1008, 1996.

R. Yan, M. J. Bienkowski, M. E. Shuck, H. Miao, M. C. Tory et al., Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity, Nature, vol.402, pp.533-537, 1999.

D. Yang, P. Stavrides, P. S. Mohan, S. Kaushik, A. Kumar et al., Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits, Brain, vol.134, pp.258-277, 2011.

W. Yang, X. Zhou, H. R. Zimmermann, D. R. Cavener, E. Klann et al., Repression of the eIF2? kinase PERK alleviates mGluR-LTD impairments in a mouse model of Alzheimer's disease, Neurobiol. Aging, vol.41, pp.19-24, 2016.

J. Ye, R. B. Rawson, R. Komuro, X. Chen, U. P. Davé et al., ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs, Mol. Cell, vol.6, pp.1355-1364, 2000.

H. Yoshida, T. Matsui, A. Yamamoto, T. Okada, and K. Mori, XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor, Cell, vol.107, pp.881-891, 2001.

S. G. Younkin and S. , The role of Ab42 in Alzheimer's disease, J Physiology, vol.92, pp.289-292, 1998.

W. H. Yu, A. M. Cuervo, A. Kumar, C. M. Peterhoff, S. D. Schmidt et al., Macroautophagy-a novel ?amyloid peptide-generating pathway activated in Alzheimer's disease, J. Cell Biol, vol.171, pp.87-98, 2005.

R. Yuste and T. Bonhoeffer, Morphological changes in dendritic spines associated with long-term synaptic plasticity, Annu. Rev. Neurosci, vol.24, pp.1071-1089, 2001.

M. Zerial and H. Mcbride, Rab proteins as membrane organizers, Nat. Rev. Mol. Cell Biol, vol.2, pp.107-117, 2001.

J. Zhou, S. Tan, V. Nicolas, C. Bauvy, N. Yang et al., Activation of lysosomal function in the course of autophagy via mTORC1 suppression and autophagosome-lysosome fusion, Cell Res, vol.23, pp.508-523, 2013.

Q. Zhou, K. J. Homma, and M. Poo, Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses, Neuron, vol.44, pp.749-757, 2004.

P. J. Zhu, W. Huang, D. Kalikulov, J. W. Yoo, A. N. Placzek et al., Suppression of PKR Promotes Network Excitability and Enhanced Cognition by Interferon-?-Mediated Disinhibition, Cell, vol.147, pp.1384-1396, 2011.

R. Zoncu, L. Bar-peled, A. Efeyan, S. Wang, Y. Sancak et al., mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase, Science, vol.334, pp.678-683, 2011.

C. Zou, E. Montagna, Y. Shi, F. Peters, L. Blazquez-llorca et al., Intraneuronal APP and extracellular A? independently cause dendritic spine pathology in transgenic mouse models of Alzheimer's disease, Acta Neuropathol. (Berl.), vol.129, pp.909-920, 2015.