A. Abbott, Laboratory animals: the Renaissance rat, Nature, vol.428, issue.6982, pp.464-466, 2004.

P. Acharya, M. L. Segall, M. Zaiou, J. Morrow, K. H. Weisgraber et al., Comparison of the stabilities and unfolding pathways of human apolipoprotein E isoforms by differential scanning calorimetry and circular dichroism, Biochim Biophys Acta, vol.1584, issue.1, pp.9-19, 2002.

T. Adayev, J. Wegiel, and Y. W. Hwang, Harmine is an ATP-competitive inhibitor for dualspecificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A), Arch Biochem Biophys, vol.507, issue.2, pp.212-218, 2011.

M. Afzal, A. M. Safer, and M. Menon, Green tea polyphenols and their potential role in health and disease, Inflammopharmacology, vol.23, issue.4, pp.151-161, 2015.

E. K. Agyare, K. M. Jaruszewski, G. L. Curran, J. T. Rosenberg, S. C. Grant et al., Engineering theranostic nanovehicles capable of targeting cerebrovascular amyloid deposits, J Control Release, vol.185, pp.121-129, 2014.

J. J. Alam, Selective Brain-Targeted Antagonism of p38 MAPKalpha Reduces Hippocampal IL1beta Levels and Improves Morris Water Maze Performance in Aged Rats, J Alzheimers Dis, vol.48, issue.1, pp.219-227, 2015.

A. Altmann, L. Tian, V. W. Henderson, and M. D. Greicius, Sex modifies the APOE-related risk of developing Alzheimer disease, Ann Neurol, vol.75, issue.4, pp.563-573, 2014.

M. Alvarez, X. Estivill, S. De-la, and L. , DYRK1A accumulates in splicing speckles through a novel targeting signal and induces speckle disassembly, J Cell Sci, vol.116, pp.3099-3107, 2003.

S. Alves, G. Churlaud, M. Audrain, K. Michaelsen-preusse, R. Fol et al., Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer's disease mice, Brain, vol.140, issue.3, pp.826-842, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01430973

L. Amniai, P. Barbier, A. Sillen, J. M. Wieruszeski, V. Peyrot et al., , 2009.

, Alzheimer disease specific phosphoepitopes of Tau interfere with assembly of tubulin but not binding to microtubules, Faseb j, vol.23, issue.4, pp.1146-1152

P. Amouyel, T. Brousseau, J. C. Fruchart, and J. Dallongeville, Apolipoprotein E-epsilon 4 allele and Alzheimer's disease, Lancet, vol.342, issue.8882, p.1309, 1993.

C. Andorfer, Y. Kress, M. Espinoza, R. Silva, K. L. Tucker et al., Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms, J Neurochem, vol.86, issue.3, pp.582-590, 2003.

S. E. Arnold, B. T. Hyman, J. Flory, A. R. Damasio, and G. W. Van-hoesen, The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease, Cereb Cortex, vol.1, issue.1, pp.103-116, 1991.

P. V. Arriagada, J. H. Growdon, E. T. Hedley-whyte, and B. T. Hyman, Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease, Neurology, vol.42, issue.3, pp.631-639, 1992.

J. R. Arron, M. M. Winslow, A. Polleri, C. P. Chang, H. Wu et al.,

N. Kim, T. Yamasaki, U. Miyakawa, I. A. Francke, G. R. Graef et al., NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21, Nature, vol.441, issue.7093, pp.595-600, 2006.

M. Audrain, R. Fol, P. Dutar, B. Potier, J. M. Billard et al., , 2016.

, Alzheimer's disease-like APP processing in wild-type mice identifies synaptic defects as initial steps of disease progression, Mol Neurodegener, vol.11, p.5

M. Audrain, B. Souchet, S. Alves, R. Fol, A. Viode et al., ?APP Processing Drives Gradual Tau Pathology in an AgeDependent Amyloid Rat Model of Alzheimer's Disease, pp.1-18, 2017.

M. Audrain, B. Souchet, S. Alves, R. Fol, A. Viode et al., betaAPP Processing Drives Gradual Tau Pathology in an AgeDependent Amyloid Rat Model of Alzheimer's Disease, pp.1-18, 2017.

J. C. Augustinack, A. Schneider, E. M. Mandelkow, and B. T. Hyman, Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease, Acta Neuropathol, vol.103, issue.1, pp.26-35, 2002.

J. Bain, H. Mclauchlan, M. Elliott, and P. Cohen, The specificities of protein kinase inhibitors: an update, Biochem J, vol.371, pp.199-204, 2003.

C. Ballard, S. Gauthier, A. Corbett, C. Brayne, D. Aarsland et al., Alzheimer's disease, Lancet, vol.377, issue.9770, pp.1019-1031, 2011.

K. Baranger, P. Giannoni, S. D. Girard, S. Girot, F. Gaven et al., Chronic treatments with a 5-HT4 receptor agonist decrease amyloid pathology in the entorhinal cortex and learning and memory deficits in the 5xFAD mouse model of Alzheimer's disease, Neuropharmacology, vol.126, pp.128-141, 2017.

L. Barbiero, L. Benussi, R. Ghidoni, A. Alberici, C. Russo et al., BACE-2 is overexpressed in Down's syndrome, Exp Neurol, vol.182, issue.2, pp.335-345, 2003.

I. Bardou, H. M. Brothers, R. M. Kaercher, S. C. Hopp, and G. L. Wenk, Differential effects of duration and age on the consequences of neuroinflammation in the hippocampus, Neurobiol Aging, vol.34, issue.10, pp.2293-2301, 2013.

V. L. Batalha, J. E. Coelho, Y. Baqi, E. Malik, E. Mariciniak et al., Beneficial effects of caffeine in a transgenic model of Alzheimer's disease-like tau pathology, Mol Psychiatry, vol.35, issue.9, pp.2079-2090, 2014.

K. A. Bates, G. Verdile, Q. X. Li, D. Ames, P. Hudson et al., Clearance mechanisms of Alzheimer's amyloid-beta peptide: implications for therapeutic design and diagnostic tests, Mol Psychiatry, vol.14, issue.5, pp.469-486, 2009.

W. Becker, Y. Weber, K. Wetzel, K. Eirmbter, F. J. Tejedor et al., Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases, J Biol Chem, vol.273, issue.40, pp.25893-25902, 1998.

M. G. Belza and H. Urich, Cerebral amyloid angiopathy in Down's syndrome, Clin Neuropathol, vol.5, issue.6, pp.257-260, 1986.

L. Ben-haim, The JAK/STAT3 pathway is a common inducer of astrocyte reactivity in Alzheimer's and Huntington's diseases, J Neurosci, vol.35, issue.6, pp.2817-2829, 2015.

D. A. Bennett, R. S. Wilson, J. A. Schneider, D. A. Evans, N. T. Aggarwal et al., Apolipoprotein E epsilon4 allele, AD pathology, and the clinical expression of Alzheimer's disease, Neurology, vol.60, issue.2, pp.246-252, 2003.

I. Bezprozvanny and M. P. Mattson, Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease, Trends Neurosci, vol.31, issue.9, pp.454-463, 2008.

L. M. Billings, S. Oddo, K. N. Green, J. L. Mcgaugh, and F. M. Laferla, Intraneuronal Abeta causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice, Neuron, vol.45, issue.5, pp.675-688, 2005.

K. Bisht, K. P. Sharma, C. Lecours, M. G. Sanchez, H. E. Hajj et al., Dark microglia: A new phenotype predominantly associated with pathological states, Glia, vol.64, issue.5, pp.826-839, 2016.

H. Braak and E. Braak, Neuropathological stageing of Alzheimer-related changes, Acta Neuropathol, vol.82, issue.4, pp.239-259, 1991.

M. Brahic, L. Bousset, G. Bieri, R. Melki, and A. D. Gitler, Axonal transport and secretion of fibrillar forms of alpha-synuclein, Abeta42 peptide and HTTExon 1, Acta Neuropathol, vol.131, issue.4, pp.539-548, 2016.

C. Branca, D. M. Shaw, R. Belfiore, V. Gokhale, A. Y. Shaw et al., Dyrk1 inhibition improves Alzheimer's disease-like pathology, Aging Cell, 2017.

N. Brooijmans, Y. W. Chang, D. Mobilio, R. A. Denny, and C. Humblet, An enriched structural kinase database to enable kinome-wide structure-based analyses and drug discovery, Protein Sci, vol.19, issue.4, pp.763-774, 2010.

D. Brooker, J. L. Fontaine, S. Evans, J. Bray, and K. Saad, Public health guidance to facilitate timely diagnosis of dementia: ALzheimer's COoperative Valuation in Europe recommendations, Int J Geriatr Psychiatry, vol.29, issue.7, pp.682-693, 2014.

X. L. Bu, Y. Xiang, W. S. Jin, J. Wang, L. L. Shen et al., Blood-derived amyloid-beta protein induces Alzheimer's disease pathologies, Mol Psychiatry, 2017.

J. L. Buescher and C. J. Phiel, A noncatalytic domain of glycogen synthase kinase-3 (GSK-3) is essential for activity, J Biol Chem, vol.285, issue.11, pp.7957-7963, 2010.

L. C. Bui, L. Tabouy, F. Busi, J. M. Dupret, N. Janel et al., A high-performance liquid chromatography assay for Dyrk1a, a Down syndromeassociated kinase, Anal Biochem, vol.449, pp.172-178, 2014.

J. E. Burda and M. V. Sofroniew, Reactive gliosis and the multicellular response to CNS damage and disease, Neuron, vol.81, issue.2, pp.229-248, 2014.

M. A. Burlot, J. Braudeau, K. Michaelsen-preusse, B. Potier, S. Ayciriex et al.,

P. Potier, M. Dutar, L. Korte, D. Buee, N. Blum et al., Cholesterol 24-hydroxylase defect is implicated in memory impairments associated with Alzheimer-like Tau pathology, Hum Mol Genet, vol.24, issue.21, pp.5965-5976, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01779042

J. Busciglio, D. H. Gabuzda, P. Matsudaira, and B. A. Yankner, Generation of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells, Proc Natl Acad Sci U S A, vol.90, issue.5, pp.2092-2096, 1993.

D. M. Bushman, G. E. Kaeser, B. Siddoway, J. W. Westra, R. R. Rivera et al., Genomic mosaicism with increased amyloid precursor protein (APP) gene copy number in single neurons from sporadic Alzheimer's disease brains, 2015.

X. D. Cai, T. E. Golde, and S. G. Younkin, Release of excess amyloid beta protein from a mutant amyloid beta protein precursor, Science, vol.259, issue.5094, pp.514-516, 1993.

M. Carter and J. Shieh, Guide to Research Techniques in Neuroscience, 2015.

M. Cascella and S. Bimonte, The efficacy of Epigallocatechin-3-gallate (green tea) in the treatment of Alzheimer's disease: an overview of pre-clinical studies and translational perspectives in clinical practice, vol.12, p.36, 2017.

C. Caspersen, N. Wang, J. Yao, A. Sosunov, X. Chen et al., Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease, Faseb j, vol.19, issue.14, pp.2040-2041, 2005.

D. L. Castillo-carranza, M. J. Guerrero-munoz, U. Sengupta, C. Hernandez, A. D. Barrett et al., Tau immunotherapy modulates both pathological tau and upstream amyloid pathology in an Alzheimer's disease mouse model, J Neurosci, vol.35, issue.12, pp.4857-4868, 2015.

A. Cattaneo, N. Cattane, S. Galluzzi, S. Provasi, N. Lopizzo et al., Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly, Neurobiol Aging, vol.49, pp.60-68, 2017.

H. Chainay, Déficit de la mémoire sémantique dans la démence de type Alzheimer, 2005.

H. Chen and S. E. Antonarakis, Localisation of a human homologue of the Drosophila mnb and rat Dyrk genes to chromosome 21q22.2, Hum Genet, vol.99, issue.2, pp.262-265, 1997.

Y. Chen, Z. Liang, J. Blanchard, C. L. Dai, S. Sun et al., A non-transgenic mouse model (icv-STZ mouse) of Alzheimer's disease: similarities to and differences from the transgenic model (3xTg-AD mouse), Mol Neurobiol, vol.47, issue.2, pp.711-725, 2013.

M. S. Cheon, M. Bajo, S. H. Kim, J. O. Claudio, A. K. Stewart et al., Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain: challenging the gene dosage effect hypothesis (Part II), Amino Acids, vol.24, issue.1-2, pp.119-125, 2003.

T. Chiba, M. Yamada, J. Sasabe, K. Terashita, M. Shimoda et al., Amyloidbeta causes memory impairment by disturbing the JAK2/STAT3 axis in hippocampal neurons, Mol Psychiatry, vol.14, issue.2, pp.206-222, 2009.

H. Cho, J. Y. Choi, M. S. Hwang, Y. J. Kim, H. M. Lee et al.,

H. Lyoo, In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum, Ann Neurol, vol.80, issue.2, pp.247-258, 2016.

I. Chumakov, P. Rigault, S. Guillou, P. Ougen, A. Billaut et al., Continuum of overlapping clones spanning the entire human chromosome 21q, Nature, vol.359, issue.6394, pp.380-387, 1992.

M. Citron, T. Oltersdorf, C. Haass, L. Mcconlogue, A. Y. Hung et al., Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production, Nature, vol.360, issue.6405, pp.672-674, 1992.

F. Clavaguera, T. Bolmont, R. A. Crowther, D. Abramowski, S. Frank et al., Transmission and spreading of tauopathy in transgenic mouse brain, Nat Cell Biol, vol.11, issue.7, pp.909-913, 2009.

P. M. Clifford, S. Zarrabi, G. Siu, K. J. Kinsler, M. C. Kosciuk et al., Abeta peptides can enter the brain through a defective blood-brain barrier and bind selectively to neurons, Brain Res, vol.1142, pp.223-236, 2007.

L. Collin, B. Bohrmann, U. Gopfert, K. Oroszlan-szovik, L. Ozmen et al., Neuronal uptake of tau/pS422 antibody and reduced progression of tau pathology in a mouse model of Alzheimer's disease, Brain, vol.137, pp.2834-2846, 2014.

A. Coppus, H. Evenhuis, G. J. Verberne, F. Visser, P. Van-gool et al., Dementia and mortality in persons with Down's syndrome, J Intellect Disabil Res, vol.50, pp.768-777, 2006.

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, issue.5123, pp.921-923, 1993.

S. Coutadeur, H. Benyamine, L. Delalonde, C. Oliveira, B. Leblond et al.,

T. Casagrande, A. Taverne, M. P. Girard, L. Pando, and . Desire, A novel DYRK1A (Dual specificity tyrosine phosphorylation-regulated kinase 1A) inhibitor for the treatment of Alzheimer's disease: effect on Tau and amyloid pathologies in vitro, J Neurochem, vol.133, issue.3, pp.440-451, 2015.

J. Cummings, G. Lee, T. Mortsdorf, A. Ritter, and K. Zhong, Alzheimer's disease drug development pipeline: 2017, Alzheimers Dement (N Y), vol.3, issue.3, pp.367-384, 2017.

B. Darocha-souto, T. C. Scotton, M. Coma, A. Serrano-pozo, T. Hashimoto et al., Brain oligomeric beta-amyloid but not total amyloid plaque burden correlates with neuronal loss and astrocyte inflammatory response in amyloid precursor protein/tau transgenic mice, J Neuropathol Exp Neurol, vol.70, issue.5, pp.360-376, 2011.

D. C. David, S. Hauptmann, I. Scherping, K. Schuessel, U. Keil et al., Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice, J Biol Chem, vol.280, issue.25, pp.23802-23814, 2005.

A. De-calignon, L. M. Fox, R. Pitstick, G. A. Carlson, B. J. Bacskai et al., Caspase activation precedes and leads to tangles, Nature, vol.464, issue.7292, pp.1201-1204, 2010.

A. De-calignon, M. Polydoro, M. Suarez-calvet, C. William, D. H. Adamowicz et al., Propagation of tau pathology in a model of early Alzheimer's disease, Neuron, vol.73, issue.4, pp.685-697, 2012.

R. De-la-torre, S. De-sola, G. Hernandez, M. Farre, J. Pujol et al.,

. Dierssen, Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial, Lancet Neurol, vol.15, issue.8, pp.801-810, 2016.

F. E. De-leeuw, F. Richard, J. C. De-groot, C. M. Van-duijn, A. Hofman et al., Interaction between hypertension, apoE, and cerebral white matter lesions, Stroke, vol.35, issue.5, pp.1057-1060, 2004.

R. Deane, S. Yan, R. K. Submamaryan, B. Larue, S. Jovanovic et al., RAGE mediates amyloidbeta peptide transport across the blood-brain barrier and accumulation in brain, Nat Med, vol.9, issue.7, pp.907-913, 2003.

M. Debdab, F. Carreaux, S. Renault, M. Soundararajan, O. Fedorov et al., Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing, J Med Chem, vol.54, issue.12, pp.4172-4186, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00870007

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, issue.5, pp.457-464, 1990.

T. Del-ser, K. C. Steinwachs, H. J. Gertz, M. V. Andres, B. Gomez-carrillo et al., Treatment of Alzheimer's disease with the GSK-3 inhibitor tideglusib: a pilot study, J Alzheimers Dis, vol.33, issue.1, pp.205-215, 2013.

J. M. Delabar, D. Theophile, Z. Rahmani, Z. Chettouh, J. L. Blouin et al., Molecular mapping of twenty-four features of Down syndrome on chromosome 21, Eur J Hum Genet, vol.1, issue.2, pp.114-124, 1993.

S. L. Devos, B. T. Corjuc, C. Commins, S. Dujardin, R. N. Bannon et al., Tau reduction in the presence of amyloid-beta prevents tau pathology and neuronal death in vivo, 2018.

M. Di-filippo, P. Sarchielli, B. Picconi, and P. Calabresi, Neuroinflammation and synaptic plasticity: theoretical basis for a novel, immune-centred, therapeutic approach to neurological disorders, Trends Pharmacol Sci, vol.29, issue.8, pp.402-412, 2008.

C. A. Dickey, J. Dunmore, B. Lu, J. W. Wang, W. C. Lee et al., HSP induction mediates selective clearance of tau phosphorylated at prolinedirected Ser/Thr sites but not KXGS (MARK) sites, Faseb j, vol.20, issue.6, pp.753-755, 2006.

R. Dixit, J. L. Ross, Y. E. Goldman, and E. L. Holzbaur, Differential regulation of dynein and kinesin motor proteins by tau, Science, vol.319, issue.5866, pp.1086-1089, 2008.

S. Do-carmo and A. C. Cuello, Modeling Alzheimer's disease in transgenic rats, Mol Neurodegener, vol.8, p.37, 2013.

N. J. Donovan, J. J. Locascio, G. A. Marshall, J. Gatchel, B. J. Hanseeuw et al., Longitudinal Association of Amyloid Beta and Anxious-Depressive Symptoms in Cognitively Normal Older Adults, Am J Psychiatry, p.201717040442, 2018.

R. S. Doody, R. Raman, M. Farlow, T. Iwatsubo, B. Vellas et al., A phase 3 trial of semagacestat for treatment of Alzheimer's disease, N Engl J Med, vol.369, issue.4, pp.341-350, 2013.

W. K. Dowjat, T. Adayev, I. Kuchna, K. Nowicki, S. Palminiello et al., Trisomy-driven overexpression of DYRK1A kinase in the brain of subjects with Down syndrome, Neurosci Lett, vol.413, issue.1, pp.77-81, 2007.

D. B. Dubal and P. M. Wise, Estrogen and neuroprotection: from clinical observations to molecular mechanisms, Dialogues Clin Neurosci, vol.4, issue.2, pp.149-161, 2002.

B. Dubois, S. Epelbaum, F. Nyasse, H. Bakardjian, G. Gagliardi et al., Cognitive and neuroimaging features and brain beta-amyloidosis in individuals at risk of Alzheimer's disease (INSIGHT-preAD): a longitudinal observational study, Lancet Neurol, 2018.

B. Dubois, H. H. Feldman, C. Jacova, S. T. Dekosky, P. Barberger-gateau et al., Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria, Lancet Neurol, vol.6, issue.8, pp.734-746, 2007.

B. Dubois, H. H. Feldman, C. Jacova, H. Hampel, J. L. Molinuevo et al., Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria, Lancet Neurol, vol.13, issue.6, pp.614-629, 2014.

B. Dubois, H. Hampel, H. H. Feldman, P. Scheltens, P. Aisen et al., Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria, Alzheimers Dement, vol.12, issue.3, pp.292-323, 2016.

C. Duyckaerts, M. C. Potier, and B. Delatour, Alzheimer disease models and human neuropathology: similarities and differences, Acta Neuropathol, vol.115, issue.1, pp.5-38, 2008.
URL : https://hal.archives-ouvertes.fr/hal-00320572

V. Echeverria, A. Ducatenzeiler, L. Alhonen, J. Janne, S. M. Grant et al., Rat transgenic models with a phenotype of intracellular Abeta accumulation in hippocampus and cortex, J Alzheimers Dis, vol.6, issue.3, pp.209-219, 2004.

P. Edison, H. A. Archer, R. Hinz, A. Hammers, N. Pavese et al., Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study, Neurology, vol.68, issue.7, pp.501-508, 2007.

S. Epelbaum, R. Genthon, E. Cavedo, M. O. Habert, F. Lamari et al., Preclinical Alzheimer's disease: A systematic review of the cohorts underlying the concept, Alzheimers Dement, vol.13, issue.4, pp.454-467, 2017.

D. Erten-lyons, H. H. Dodge, R. Woltjer, L. C. Silbert, D. B. Howieson et al., Neuropathologic basis of age-associated brain atrophy, JAMA Neurol, vol.70, issue.5, pp.616-622, 2013.

M. M. Esiri, Ageing and the brain, J Pathol, vol.211, issue.2, pp.181-187, 2007.

L. A. Farrer, L. A. Cupples, J. L. Haines, B. Hyman, W. A. Kukull et al., Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium, Jama, vol.278, issue.16, pp.1349-1356, 1997.

A. Ferreira and E. H. Bigio, Calpain-mediated tau cleavage: a mechanism leading to neurodegeneration shared by multiple tauopathies, Mol Med, vol.17, issue.7-8, pp.676-685, 2011.

S. T. Ferreira, M. V. Lourenco, M. M. Oliveira, and F. G. De-felice, Soluble amyloid-beta oligomers as synaptotoxins leading to cognitive impairment in Alzheimer's disease, Front Cell Neurosci, vol.9, p.191, 2015.

I. Ferrer, M. Barrachina, B. Puig, M. Martinez-de-lagran, E. Marti et al., Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models, Neurobiol Dis, vol.20, issue.2, pp.392-400, 2005.

C. E. Finch, The biology of aging in model organisms, Alzheimer Dis Assoc Disord, vol.17, pp.39-41, 2003.

C. E. Finch and R. M. Sapolsky, The evolution of Alzheimer disease, the reproductive schedule, and apoE isoforms, Neurobiol Aging, vol.20, issue.4, pp.407-428, 1999.

D. Fischer, M. D. Mukrasch, J. Biernat, S. Bibow, M. Blackledge et al., Conformational changes specific for pseudophosphorylation at serine 262 selectively impair binding of tau to microtubules, Biochemistry, vol.48, issue.42, pp.10047-10055, 2009.

D. G. Flood, Y. G. Lin, D. M. Lang, S. P. Trusko, J. D. Hirsch et al.,

. Howland, A transgenic rat model of Alzheimer's disease with extracellular Abeta deposition, Neurobiol Aging, vol.30, issue.7, pp.1078-1090, 2009.

R. Fol, J. Braudeau, S. Ludewig, T. Abel, S. W. Weyer et al., Viral gene transfer of APPsalpha rescues synaptic failure in an Alzheimer's disease mouse model, Acta Neuropathol, 2015.

R. Folkesson, K. Malkiewicz, E. Kloskowska, T. Nilsson, E. Popova et al., A transgenic rat expressing human APP with the Swedish Alzheimer's disease mutation, Biochem Biophys Res Commun, vol.358, issue.3, pp.777-782, 2007.

M. F. Folstein, S. E. Folstein, and P. R. Mchugh, Mini-mental state". A practical method for grading the cognitive state of patients for the clinician, J Psychiatr Res, vol.12, issue.3, pp.189-198, 1975.

L. Forny-germano, N. M. Lyra-e-silva, A. F. Batista, J. Brito-moreira, and M. Gralle, Alzheimer's disease-like pathology induced by amyloid-beta oligomers in nonhuman primates, vol.34, pp.13629-13643, 2014.

S. Frank, G. J. Burbach, M. Bonin, M. Walter, W. Streit et al., TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice, Glia, vol.56, issue.13, pp.1438-1447, 2008.

M. Garcia-alloza, E. M. Robbins, S. X. Zhang-nunes, S. M. Purcell, R. A. Betensky et al.,

B. J. Greenberg, M. P. Bacskai, and . Frosch, Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease, Neurobiol Dis, vol.24, issue.3, pp.516-524, 2006.

J. Ghiso, M. Shayo, M. Calero, D. Ng, Y. Tomidokoro et al., Systemic catabolism of Alzheimer's Abeta40 and Abeta42, J Biol Chem, vol.279, issue.44, pp.45897-45908, 2004.

P. Giannakopoulos, F. R. Herrmann, T. Bussiere, C. Bouras, E. Kovari et al., Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease, Neurology, vol.60, issue.9, pp.1495-1500, 2003.

L. Gimenez-llort, G. Rivera-hernandez, M. Marin-argany, J. L. Sanchez-quesada, and S. Villegas, Early intervention in the 3xTg-AD mice with an amyloid beta-antibody fragment ameliorates first hallmarks of Alzheimer disease, MAbs, vol.5, issue.5, pp.665-677, 2013.

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, issue.3, 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, issue.6311, pp.704-706, 1991.

N. Gockler, G. Jofre, C. Papadopoulos, U. Soppa, F. J. Tejedor et al., Harmine specifically inhibits protein kinase DYRK1A and interferes with neurite formation, Febs j, vol.276, issue.21, pp.6324-6337, 2009.

S. Godeluck, Les médicaments contre Alzheimer ne seront plus remboursés à compter du 1er août, 2018.

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, issue.4791, pp.877-880, 1987.

T. Gomez-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, issue.1, pp.17-24, 1997.

B. L. Goode and S. C. Feinstein, Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tau, J Cell Biol, vol.124, issue.5, pp.769-782, 1994.

J. Gotz, F. Chen, J. Van-dorpe, and R. M. Nitsch, Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils, Science, vol.293, issue.5534, pp.1491-1495, 2001.

J. Gotz and L. M. Ittner, Animal models of Alzheimer's disease and frontotemporal dementia, Nat Rev Neurosci, vol.9, issue.7, pp.532-544, 2008.

J. Gotz, A. Probst, M. G. Spillantini, T. Schafer, R. Jakes et al., Somatodendritic localization and hyperphosphorylation of tau protein in transgenic mice expressing the longest human brain tau isoform, Embo j, vol.14, issue.7, pp.1304-1313, 1995.

G. K. Gouras, J. Tsai, J. Naslund, B. Vincent, M. Edgar et al., Intraneuronal Abeta42 accumulation in human brain, Am J Pathol, vol.156, issue.1, pp.15-20, 2000.

S. G. Greenberg, P. Davies, J. D. Schein, and L. I. Binder, Hydrofluoric acid-treated tau PHF proteins display the same biochemical properties as normal tau, J Biol Chem, vol.267, issue.1, pp.564-569, 1992.

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, issue.13, pp.4913-4917, 1986.

F. Guedj, P. L. Pereira, S. Najas, M. J. Barallobre, C. Chabert et al., DYRK1A: a master regulatory protein controlling brain growth, Neurobiol Dis, vol.46, issue.1, pp.190-203, 2012.

F. Guedj, C. Sebrie, I. Rivals, A. Ledru, E. Paly et al., Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A, PLoS One, vol.4, issue.2, p.4606, 2009.

R. Guerreiro, A. Wojtas, J. Bras, M. Carrasquillo, E. Rogaeva et al.,

S. Kauwe, L. Younkin, J. Hazrati, J. Collinge, T. Pocock et al., TREM2 variants in Alzheimer's disease, vol.368, pp.117-127, 2013.

J. Guimera, C. Casas, X. Estivill, and M. Pritchard, Human minibrain homologue (MNBH/DYRK1): characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome, Genomics, vol.57, issue.3, pp.407-418, 1999.

J. Guimera, C. Casas, C. Pucharcos, A. Solans, A. Domenech et al., A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region, Hum Mol Genet, vol.5, issue.9, pp.1305-1310, 1996.

K. A. Gyure, R. Durham, W. F. Stewart, J. E. Smialek, and J. C. Troncoso, Intraneuronal abetaamyloid precedes development of amyloid plaques in Down syndrome, Arch Pathol Lab Med, vol.125, issue.4, pp.489-492, 2001.

C. Haass and D. J. Selkoe, Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide, Nat Rev Mol Cell Biol, vol.8, issue.2, pp.101-112, 2007.

L. Hamelin, J. Lagarde, G. Dorothee, C. Leroy, M. Labit et al.,

M. Dauphinot, B. Bertoux, P. Dubois, O. Gervais, M. C. Colliot et al., Early and protective microglial activation in Alzheimer's disease: a prospective study using 18F-DPA-714 PET imaging, Brain, vol.139, pp.1252-1264, 2016.

B. Hammerle, C. Elizalde, J. Galceran, W. Becker, and F. J. Tejedor, The MNB/DYRK1A protein kinase: neurobiological functions and Down syndrome implications, J Neural Transm Suppl, issue.67, pp.129-137, 2003.

B. Hammerle, C. Elizalde, and F. J. Tejedor, The spatio-temporal and subcellular expression of the candidate Down syndrome gene Mnb/Dyrk1A in the developing mouse brain suggests distinct sequential roles in neuronal development, Eur J Neurosci, vol.27, issue.5, pp.1061-1074, 2008.

S. K. Hanks and T. Hunter, Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification, Faseb j, vol.9, issue.8, pp.576-596, 1995.

S. K. Hanks and A. M. Quinn, Protein kinase catalytic domain sequence database: identification of conserved features of primary structure and classification of family members, Methods Enzymol, vol.200, pp.38-62, 1991.

S. K. Hanks, A. M. Quinn, and T. Hunter, The protein kinase family: conserved features and deduced phylogeny of the catalytic domains, Science, vol.241, issue.4861, pp.42-52, 1988.

G. E. Hardingham and H. Bading, Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders, Nat Rev Neurosci, vol.11, issue.10, pp.682-696, 2010.

J. Hardy and D. Allsop, Amyloid deposition as the central event in the aetiology of Alzheimer's disease, Trends Pharmacol Sci, vol.12, issue.10, pp.383-388, 1991.

J. Hardy and D. J. Selkoe, The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics, Science, vol.297, issue.5580, pp.353-356, 2002.

J. A. Hardy and G. A. Higgins, Alzheimer's disease: the amyloid cascade hypothesis, Science, vol.256, issue.5054, pp.184-185, 1992.

T. Hartmann, S. C. Bieger, B. Bruhl, P. J. Tienari, N. Ida et al.,

K. Dotti, K. Unsicker, and . Beyreuther, Distinct sites of intracellular production for Alzheimer's disease A beta40/42 amyloid peptides, Nat Med, vol.3, issue.9, pp.1016-1020, 1997.

M. Hashiguchi, K. Sobue, and H. K. Paudel, 14-3-3zeta is an effector of tau protein phosphorylation, J Biol Chem, vol.275, issue.33, pp.25247-25254, 2000.

R. J. Hatch, Y. Wei, D. Xia, and J. Gotz, Hyperphosphorylated tau causes reduced hippocampal CA1 excitability by relocating the axon initial segment, Acta Neuropathol, vol.133, issue.5, pp.717-730, 2017.

J. V. Haure-mirande, M. Audrain, T. Fanutza, S. H. Kim, W. L. Klein et al.,

R. D. Dudley, M. Blitzer, B. Wang, E. E. Zhang, S. Schadt et al., Deficiency of TYROBP, an adapter protein for TREM2 and CR3 receptors, is neuroprotective in a mouse model of early Alzheimer's pathology, Acta Neuropathol, 2017.

E. Head, I. T. Lott, D. Patterson, E. Doran, and R. J. Haier, Possible compensatory events in adult Down syndrome brain prior to the development of Alzheimer disease neuropathology: targets for nonpharmacological intervention, J Alzheimers Dis, vol.11, issue.1, pp.61-76, 2007.

E. Head, I. T. Lott, D. M. Wilcock, and C. A. Lemere, Aging in Down Syndrome and the Development of Alzheimer's Disease Neuropathology, Curr Alzheimer Res, vol.13, issue.1, pp.18-29, 2016.

M. H. Heim, The Jak-STAT pathway: cytokine signalling from the receptor to the nucleus, J Recept Signal Transduct Res, vol.19, issue.1-4, pp.75-120, 1999.

C. Helmer, K. Peres, A. Pariente, F. Pasquier, S. Auriacombe et al., Primary and secondary care consultations in elderly demented individuals in France. Results from the Three-City Study, Dement Geriatr Cogn Disord, vol.26, issue.5, pp.407-415, 2008.

M. T. Heneka, M. J. Carson, J. E. Khoury, G. E. Landreth, F. Brosseron et al.,

V. H. Shinohara, C. Perry, N. G. Holmes, D. J. Bazan, S. Brooks et al., Neuroinflammation in Alzheimer's disease, Lancet Neurol, vol.14, issue.4, pp.388-405, 2015.

M. T. Heneka, M. P. Kummer, and E. Latz, Innate immune activation in neurodegenerative disease, Nat Rev Immunol, vol.14, issue.7, pp.463-477, 2014.

M. T. Heneka, M. Sastre, L. Dumitrescu-ozimek, I. Dewachter, J. Walter et al., Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice, J Neuroinflammation, vol.2, p.22, 2005.

F. L. Heppner, R. M. Ransohoff, and B. Becher, Immune attack: the role of inflammation in Alzheimer disease, Nat Rev Neurosci, vol.16, issue.6, pp.358-372, 2015.

K. Herrup, The case for rejecting the amyloid cascade hypothesis, Nat Neurosci, vol.18, issue.6, pp.794-799, 2015.

S. E. Hickman, E. K. Allison, and J. E. Khoury, Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer's disease mice, J Neurosci, vol.28, issue.33, pp.8354-8360, 2008.

L. S. Higgins, R. Catalano, D. Quon, and B. Cordell, Transgenic mice expressing human beta-APP751, but not mice expressing beta-APP695, display early Alzheimer's disease-like histopathology, Ann N Y Acad Sci, vol.695, pp.224-227, 1993.

M. Higuchi, T. Ishihara, B. Zhang, M. Hong, A. Andreadis et al., Transgenic mouse model of tauopathies with glial pathology and nervous system degeneration, Neuron, vol.35, issue.3, pp.433-446, 2002.

S. Himpel, P. Panzer, K. Eirmbter, H. Czajkowska, M. Sayed et al., Identification of the autophosphorylation sites and characterization of their effects in the protein kinase DYRK1A, Biochem J, vol.359, pp.497-505, 2001.

C. Holmes, D. Boche, D. Wilkinson, G. Yadegarfar, V. Hopkins et al., Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial, Lancet, vol.372, issue.9634, pp.216-223, 2008.

C. Holmes, C. Cunningham, E. Zotova, J. Woolford, C. Dean et al., Systemic inflammation and disease progression in Alzheimer disease, Neurology, vol.73, issue.10, pp.768-774, 2009.

E. Hone, I. J. Martins, J. Fonte, and R. N. Martins, Apolipoprotein E influences amyloid-beta clearance from the murine periphery, J Alzheimers Dis, vol.5, issue.1, pp.1-8, 2003.

S. R. Hubbard, Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog, Embo j, vol.16, issue.18, pp.5572-5581, 1997.

S. R. Hubbard and W. T. Miller, Receptor tyrosine kinases: mechanisms of activation and signaling, Curr Opin Cell Biol, vol.19, issue.2, pp.117-123, 2007.

M. Huse and J. Kuriyan, The conformational plasticity of protein kinases, Cell, vol.109, issue.3, pp.275-282, 2002.

B. T. Hyman, G. W. Van-hoesen, A. R. Damasio, and C. L. Barnes, Alzheimer's disease: cellspecific pathology isolates the hippocampal formation, Science, vol.225, issue.4667, pp.1168-1170, 1984.

M. Ikeda, K. Hirayanagi, M. Arai, S. Kakuda, K. Makioka et al., Encephalopathy with amyloid angiopathy and numerous amyloid plaques with low levels of CSF Abeta1-40/Abeta1-42, Amyloid, vol.19, issue.4, pp.186-190, 2012.

K. Iqbal, C. A. Adel, S. Chen, M. O. Chohan, E. El-akkad et al., Tau pathology in Alzheimer disease and other tauopathies, Biochim Biophys Acta, vol.1739, issue.2-3, pp.198-210, 2005.

K. Iqbal, I. Grundke-iqbal, T. Zaidi, P. A. Merz, G. Y. Wen et al., Defective brain microtubule assembly in Alzheimer's disease, Lancet, vol.2, issue.8504, pp.421-426, 1986.

A. Ittner, S. W. Chua, J. Bertz, A. Volkerling, J. Van-der-hoven et al.,

C. H. Hummel, S. Stevens, L. S. Ippati, A. Suh, G. Macmillan et al.,

A. Mackay, F. Poljak, Y. D. Delerue, L. M. Ke, and . Ittner, Site-specific phosphorylation of tau inhibits amyloid-beta toxicity in Alzheimer's mice, Science, vol.354, issue.6314, pp.904-908, 2016.

L. M. Ittner, T. Fath, Y. D. Ke, M. Bi, J. Van-eersel et al., Parkinsonism and impaired axonal transport in a mouse model of frontotemporal dementia, Proc Natl Acad Sci U S A, vol.105, issue.41, pp.15997-16002, 2008.

L. M. Ittner, Y. D. Ke, F. Delerue, M. Bi, A. Gladbach et al.,

I. A. Christie, A. Napier, M. Eckert, E. Staufenbiel, J. Hardeman et al., Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models, Cell, vol.142, issue.3, pp.387-397, 2010.

C. R. Jack, D. S. Jr, W. J. Knopman, R. C. Jagust, M. W. Petersen et al., Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers, Lancet Neurol, vol.12, issue.2, pp.207-216, 2013.

C. R. Jack, D. S. Jr, W. J. Knopman, L. M. Jagust, P. S. Shaw et al., Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade, Lancet Neurol, vol.9, issue.1, pp.119-128, 2010.

C. R. Jack, T. M. Jr, H. J. Therneau, S. D. Wiste, D. S. Weigand et al., Transition rates between amyloid and neurodegeneration biomarker states and to dementia: a population-based, longitudinal cohort study, Lancet Neurol, vol.15, issue.1, pp.56-64, 2016.

N. Janel, P. Alexopoulos, A. Badel, F. Lamari, A. C. Camproux et al., Combined assessment of DYRK1A, BDNF and homocysteine levels as diagnostic marker for Alzheimer's disease, Transl Psychiatry, vol.7, issue.6, p.1154, 2017.

N. Janel, M. Sarazin, F. Corlier, H. Corne, L. C. Souza et al., Plasma DYRK1A as a novel risk factor for Alzheimer's disease, Transl Psychiatry, vol.4, p.425, 2014.

S. M. Jang, S. Azebi, G. Soubigou, and C. Muchardt, DYRK1A phoshorylates histone H3 to differentially regulate the binding of HP1 isoforms and antagonize HP1-mediated transcriptional repression, EMBO Rep, vol.15, issue.6, pp.686-694, 2014.

J. L. Jankowsky, D. J. Fadale, J. Anderson, G. M. Xu, V. Gonzales et al., Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase, Hum Mol Genet, vol.13, issue.2, pp.159-170, 2004.

J. L. Jankowsky, L. H. Younkin, V. Gonzales, D. J. Fadale, H. H. Slunt et al., Rodent A beta modulates the solubility and distribution of amyloid deposits in transgenic mice, J Biol Chem, vol.282, issue.31, pp.22707-22720, 2007.

N. Jin, X. Yin, J. Gu, X. Zhang, J. Shi et al.,

. Liu, Truncation and Activation of Dual Specificity Tyrosine Phosphorylation-regulated Kinase 1A by Calpain I: A MOLECULAR MECHANISM LINKED TO TAU PATHOLOGY IN ALZHEIMER DISEASE, J Biol Chem, vol.290, issue.24, pp.15219-15237, 2015.

T. Jonsson, H. Stefansson, S. Steinberg, I. Jonsdottir, P. V. Jonsson et al., Variant of TREM2 associated with the risk of Alzheimer's disease, N Engl J Med, vol.368, issue.2, pp.107-116, 2013.

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, issue.6106, pp.733-736, 1987.

H. Kentrup, W. Becker, J. Heukelbach, A. Wilmes, A. Schurmann et al., Dyrk, a dual specificity protein kinase with unique structural features whose activity is dependent on tyrosine residues between subdomains VII and VIII, J Biol Chem, vol.271, issue.7, pp.3488-3495, 1996.

M. Kervern, A. Angeli, O. Nicole, F. Leveille, B. Parent et al., Selective impairment of some forms of synaptic plasticity by oligomeric amyloid-beta peptide in the mouse hippocampus: implication of extrasynaptic NMDA receptors, J Alzheimers Dis, vol.32, issue.1, pp.183-196, 2012.

H. Kettenmann, U. K. Hanisch, M. Noda, and A. Verkhratsky, Physiology of microglia, Physiol Rev, vol.91, issue.2, pp.461-553, 2011.

B. Khor, J. D. Gagnon, G. Goel, M. I. Roche, K. L. Conway et al.,

J. J. Restifo, B. D. Shea, A. F. Medoff, S. L. Shamji, A. H. Schreiber et al., The kinase DYRK1A reciprocally regulates the differentiation of Th17 and regulatory T cells, 2015.

M. Kidd, Paired helical filaments in electron microscopy of Alzheimer's disease, Nature, vol.197, pp.192-193, 1963.

I. Kii, Y. Sumida, T. Goto, R. Sonamoto, Y. Okuno et al., Selective inhibition of the kinase DYRK1A by targeting its folding process, Nat Commun, vol.7, p.11391, 2016.

H. Kim, S. O. Sablin, and R. R. Ramsay, Inhibition of monoamine oxidase A by beta-carboline derivatives, Arch Biochem Biophys, vol.337, issue.1, pp.137-142, 1997.

S. H. Kim, R. Vlkolinsky, N. Cairns, M. Fountoulakis, and G. Lubec, The reduction of NADH ubiquinone oxidoreductase 24-and 75-kDa subunits in brains of patients with Down syndrome and Alzheimer's disease, Life Sci, vol.68, issue.24, pp.2741-2750, 2001.

R. Kimura, K. Kamino, M. Yamamoto, A. Nuripa, T. Kida et al., The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease, Hum Mol Genet, vol.16, issue.1, pp.15-23, 2007.

R. Kimura and M. Ohno, Impairments in remote memory stabilization precede hippocampal synaptic and cognitive failures in 5XFAD Alzheimer mouse model, Neurobiol Dis, vol.33, issue.2, pp.229-235, 2009.

M. Kitazawa, R. Medeiros, and F. M. Laferla, Transgenic mouse models of Alzheimer disease: developing a better model as a tool for therapeutic interventions, Curr Pharm Des, vol.18, issue.8, pp.1131-1147, 2012.

E. Kloskowska, T. M. Pham, T. Nilsson, S. Zhu, J. Oberg et al., Cognitive impairment in the Tg6590 transgenic rat model of Alzheimer's disease, J Cell Mol Med, vol.14, issue.6b, pp.1816-1823, 2010.

H. H. Klunemann, W. Fronhofer, H. Wurster, W. Fischer, B. Ibach et al., Alzheimer's second patient: Johann F. and his family, Ann Neurol, vol.52, issue.4, pp.520-523, 2002.

V. Kohli, W. Gao, C. A. Camargo, J. , and P. A. Clavien, Calpain is a mediator of preservationreperfusion injury in rat liver transplantation, Proc Natl Acad Sci U S A, vol.94, issue.17, pp.9354-9359, 1997.

A. M. Koivisto, I. Hallikainen, T. Valimaki, K. Hongisto, A. Hiltunen et al., Early psychosocial intervention does not delay institutionalization in persons with mild Alzheimer disease and has impact on neither disease progression nor caregivers' well-being: ALSOVA 3-year follow-up, Int J Geriatr Psychiatry, vol.31, issue.3, pp.273-283, 2016.

E. Kojro and F. Fahrenholz, The non-amyloidogenic pathway: structure and function of alphasecretases, Subcell Biochem, vol.38, pp.105-127, 2005.

A. Kondo, K. Shahpasand, R. Mannix, J. Qiu, J. Moncaster et al., Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy, Nature, vol.523, issue.7561, pp.431-436, 2015.

E. Kontsekova, N. Zilka, B. Kovacech, R. Skrabana, and M. Novak, Identification of structural determinants on tau protein essential for its pathological function: novel therapeutic target for tau immunotherapy in Alzheimer's disease, Alzheimers Res Ther, vol.6, issue.4, p.45, 2014.

K. J. Kopeikina, B. T. Hyman, and T. L. Spires-jones, Soluble forms of tau are toxic in Alzheimer's disease, Transl Neurosci, vol.3, issue.3, pp.223-233, 2012.

A. P. Kornev and S. S. Taylor, Defining the conserved internal architecture of a protein kinase, Biochim Biophys Acta, vol.1804, issue.3, pp.440-444, 2010.

P. Krolak-salmon, Quelle place pour les biomarqueurs dans le diagnostic de la maladie d'Alzheimer et des maladies apparentées ?, Psychol NeuroPsychiatr Vieil, vol.8, issue.1, pp.25-31, 2010.

N. Kurabayashi, M. D. Nguyen, and K. Sanada, DYRK1A overexpression enhances STAT activity and astrogliogenesis in a Down syndrome mouse model, EMBO Rep, vol.16, issue.11, pp.1548-1562, 2015.

K. Kurbatskaya, E. C. Phillips, C. L. Croft, G. Dentoni, M. M. Hughes et al., Upregulation of calpain activity precedes tau phosphorylation and loss of synaptic proteins in Alzheimer's disease brain, vol.4, p.34, 2016.

M. A. Kurt, D. C. Davies, M. Kidd, K. Duff, and D. R. Howlett, Hyperphosphorylated tau and paired helical filament-like structures in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes, Neurobiol Dis, vol.14, issue.1, pp.89-97, 2003.

F. M. Laferla, K. N. Green, and S. Oddo, Intracellular amyloid-beta in Alzheimer's disease, Nat Rev Neurosci, vol.8, issue.7, pp.499-509, 2007.

J. B. Langbaum, A. S. Fleisher, K. Chen, N. Ayutyanont, F. Lopera et al., Ushering in the study and treatment of preclinical Alzheimer disease, Nat Rev Neurol, vol.9, issue.7, pp.371-381, 2013.

S. Languille, S. Blanc, O. Blin, C. I. Canale, A. Dal-pan et al., The grey mouse lemur: a non-human primate model for ageing studies, Ageing Res Rev, vol.11, issue.1, pp.150-162, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00650159

C. A. Lasagna-reeves, D. L. Castillo-carranza, U. Sengupta, A. L. Clos, G. R. Jackson et al., Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice, Mol Neurodegener, vol.6, p.39, 2011.

D. T. Laskowitz, H. Sheng, R. D. Bart, K. A. Joyner, A. D. Roses et al., , 1997.

, Apolipoprotein E-deficient mice have increased susceptibility to focal cerebral ischemia, J Cereb Blood Flow Metab, vol.17, issue.7, pp.753-758

C. Laurent, S. Burnouf, and B. Ferry, A2A adenosine receptor deletion is protective in a mouse model of Tauopathy, vol.21, pp.97-107, 2016.

O. Lazarov, G. A. Morfini, G. Pigino, A. Gadadhar, X. Chen et al., Impairments in fast axonal transport and motor neuron deficits in transgenic mice expressing familial Alzheimer's disease-linked mutant presenilin 1, J Neurosci, vol.27, issue.26, pp.7011-7020, 2007.

C. Lecoutey, D. Hedou, T. Freret, P. Giannoni, F. Gaven et al., Design of donecopride, a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer's disease treatment, vol.111, pp.3825-3830, 2014.

J. E. Lee and P. L. Han, An update of animal models of Alzheimer disease with a reevaluation of plaque depositions, Exp Neurobiol, vol.22, issue.2, pp.84-95, 2013.

M. S. Lee, S. C. Kao, C. A. Lemere, W. Xia, H. C. Tseng et al., APP processing is regulated by cytoplasmic phosphorylation, J Cell Biol, vol.163, issue.1, pp.83-95, 2003.

M. S. Lee, Y. T. Kwon, M. Li, J. Peng, R. M. Friedlander et al., Neurotoxicity induces cleavage of p35 to p25 by calpain, Nature, vol.405, issue.6784, pp.360-364, 2000.

C. L. Leibson, W. A. Rocca, V. A. Hanson, R. Cha, E. Kokmen et al., The risk of dementia among persons with diabetes mellitus: a population-based cohort study, Ann N Y Acad Sci, vol.826, pp.422-427, 1997.

W. C. Leon, F. Canneva, V. Partridge, S. Allard, M. T. Ferretti et al., A novel transgenic rat model with a full Alzheimer's-like amyloid pathology displays pre-plaque intracellular amyloid-beta-associated cognitive impairment, J Alzheimers Dis, vol.20, issue.1, pp.113-126, 2010.

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, issue.5226, pp.973-977, 1995.

E. Levy, M. D. Carman, I. J. Fernandez-madrid, M. D. Power, I. Lieberburg et al., Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type, Science, vol.248, issue.4959, pp.1124-1126, 1990.

J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral et al., Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP, Science, vol.293, issue.5534, pp.1487-1491, 2001.

J. Lewis, E. Mcgowan, J. Rockwood, H. Melrose, P. Nacharaju et al., Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein, Nat Genet, vol.25, issue.4, pp.402-405, 2000.

C. Li and J. Gotz, Somatodendritic accumulation of Tau in Alzheimer's disease is promoted by Fyn-mediated local protein translation, vol.36, pp.3120-3138, 2017.

S. Li, M. Jin, T. Koeglsperger, N. E. Shepardson, G. M. Shankar et al., Soluble Abeta oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors, J Neurosci, vol.31, issue.18, pp.6627-6638, 2011.

X. Li, Y. Kumar, H. Zempel, E. M. Mandelkow, J. Biernat et al., Novel diffusion barrier for axonal retention of Tau in neurons and its failure in neurodegeneration, Embo j, vol.30, issue.23, pp.4825-4837, 2011.

S. A. Liddelow, K. A. Guttenplan, L. E. Clarke, F. C. Bennett, C. J. Bohlen et al., Neurotoxic reactive astrocytes are induced by activated microglia, Nature, vol.541, issue.7638, pp.481-487, 2017.

R. A. Lindberg, A. M. Quinn, and T. Hunter, Dual-specificity protein kinases: will any hydroxyl do?, Trends Biochem Sci, vol.17, issue.3, pp.114-119, 1992.

C. C. Liu, C. W. Tsai, F. Deak, J. Rogers, M. Penuliar et al., Deficiency in LRP6-mediated Wnt signaling contributes to synaptic abnormalities and amyloid pathology in Alzheimer's disease, Neuron, vol.84, issue.1, pp.63-77, 2014.

F. Liu, Z. Liang, J. Wegiel, Y. W. Hwang, K. Iqbal et al., Overexpression of Dyrk1A contributes to neurofibrillary degeneration in Down syndrome, Faseb j, vol.22, issue.9, pp.3224-3233, 2008.

P. A. Lochhead, G. Sibbet, N. Morrice, and V. Cleghon, Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs, Cell, vol.121, issue.6, pp.925-936, 2005.

E. M. Lopez, K. F. Bell, A. Ribeiro-da-silva, and A. C. Cuello, Early changes in neurons of the hippocampus and neocortex in transgenic rats expressing intracellular human a-beta, J Alzheimers Dis, vol.6, issue.4, pp.443-429, 2004.

R. Love, Good fats prevent dendritic damage in mouse model of AD, Lancet Neurol, vol.3, issue.11, p.636, 2004.

S. Love and J. S. Miners, Cerebrovascular disease in ageing and Alzheimer's disease, Acta Neuropathol, vol.131, issue.5, pp.645-658, 2016.

J. A. Luchsinger, M. X. Tang, Y. Stern, S. Shea, and R. Mayeux, Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort, Am J Epidemiol, vol.154, issue.7, pp.635-641, 2001.

L. F. Lue, Y. M. Kuo, A. E. Roher, L. Brachova, Y. Shen et al., Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease, Am J Pathol, vol.155, issue.3, pp.853-862, 1999.

J. Luna-munoz, L. Chavez-macias, F. Garcia-sierra, and R. Mena, Earliest stages of tau conformational changes are related to the appearance of a sequence of specific phospho-dependent tau epitopes in Alzheimer's disease, J Alzheimers Dis, vol.12, issue.4, pp.365-375, 2007.

I. R. Mackenzie, R. S. Mclachlan, C. S. Kubu, and L. A. Miller, Prospective neuropsychological assessment of nondemented patients with biopsy proven senile plaques, Neurology, vol.46, issue.2, pp.425-429, 1996.

J. B. Mackic, J. Bading, J. Ghiso, L. Walker, T. Wisniewski et al., Circulating amyloid-beta peptide crosses the blood-brain barrier in aged monkeys and contributes to Alzheimer's disease lesions, Vascul Pharmacol, vol.38, issue.6, pp.303-313, 2002.

F. Magara, U. Muller, Z. W. Li, H. P. Lipp, C. Weissmann et al., Genetic background changes the pattern of forebrain commissure defects in transgenic mice underexpressing the beta-amyloid-precursor protein, Proc Natl Acad Sci U S A, vol.96, issue.8, pp.4656-4661, 1999.

S. Mandrekar, Q. Jiang, C. Y. Lee, J. Koenigsknecht-talboo, D. M. Holtzman et al., Microglia mediate the clearance of soluble Abeta through fluid phase macropinocytosis, J Neurosci, vol.29, issue.13, pp.4252-4262, 2009.

D. M. Mann and M. M. Esiri, The pattern of acquisition of plaques and tangles in the brains of patients under 50 years of age with Down's syndrome, J Neurol Sci, vol.89, issue.2-3, pp.169-179, 1989.

G. Manning, D. B. Whyte, R. Martinez, T. Hunter, and S. Sudarsanam, The protein kinase complement of the human genome, Science, vol.298, issue.5600, pp.1912-1934, 2002.

N. Maphis, G. Xu, O. N. Kokiko-cochran, S. Jiang, A. Cardona et al.,

. Bhaskar, Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain, Brain, vol.138, pp.1738-1755, 2015.

M. L. Margallo-lana, P. B. Moore, D. W. Kay, R. H. Perry, B. E. Reid et al., Fifteen-year follow-up of 92 hospitalized adults with Down's syndrome: incidence of cognitive decline, its relationship to age and neuropathology, J Intellect Disabil Res, vol.51, pp.463-477, 2007.

M. G. Marmot, G. D. Smith, S. Stansfeld, C. Patel, F. North et al., Health inequalities among British civil servants: the Whitehall II study, Lancet, vol.337, pp.1387-1393, 1991.

E. Marti, X. Altafaj, M. Dierssen, S. De-la-luna, V. Fotaki et al.,

. Estivill, Dyrk1A expression pattern supports specific roles of this kinase in the adult central nervous system, Brain Res, vol.964, issue.2, pp.250-263, 2003.

L. Martin, X. Latypova, and F. Terro, Post-translational modifications of tau protein: implications for Alzheimer's disease, Neurochem Int, vol.58, issue.4, pp.458-471, 2011.

E. Masliah, Mechanisms of synaptic dysfunction in Alzheimer's disease, Histol Histopathol, vol.10, issue.2, pp.509-519, 1995.

E. Masliah, A. Sisk, M. Mallory, and D. Games, Neurofibrillary pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein, J Neuropathol Exp Neurol, vol.60, issue.4, pp.357-368, 2001.

C. L. Masters and K. Beyreuther, Neuronal origin of cerebral amyloidogenic proteins: their role in Alzheimer's disease and unconventional virus diseases of the nervous system, Ciba Found Symp, vol.126, pp.49-64, 1987.

M. P. Mattson, B. Cheng, A. R. Culwell, F. S. Esch, I. Lieberburg et al., Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the beta-amyloid precursor protein, Neuron, vol.10, issue.2, pp.243-254, 1993.

T. Maurice, B. P. Lockhart, and A. Privat, Amnesia induced in mice by centrally administered betaamyloid peptides involves cholinergic dysfunction, Brain Res, vol.706, issue.2, pp.181-193, 1996.

M. P. Mazanetz and P. M. Fischer, Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases, Nat Rev Drug Discov, vol.6, issue.6, pp.464-479, 2007.

D. Mccade, G. Savage, and S. L. Naismith, Review of emotion recognition in mild cognitive impairment, Dement Geriatr Cogn Disord, vol.32, issue.4, pp.257-266, 2011.

E. Mcdade and R. J. Bateman, Stop Alzheimer's before it starts, Nature, vol.547, issue.7662, pp.153-155, 2017.

S. D. Mcelyea, J. M. Starbuck, D. M. Tumbleson-brink, E. Harrington, J. D. Blazek et al., Influence of prenatal EGCG treatment and Dyrk1a dosage reduction on craniofacial features associated with Down syndrome, Hum Mol Genet, vol.25, issue.22, pp.4856-4869, 2016.

P. L. Mcgeer and E. G. Mcgeer, Targeting microglia for the treatment of Alzheimer's disease, Expert Opin Ther Targets, vol.19, issue.4, pp.497-506, 2015.

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, issue.6, pp.860-866, 1999.

R. Medeiros, M. Kitazawa, M. A. Chabrier, D. Cheng, D. Baglietto-vargas et al., Calpain inhibitor A-705253 mitigates Alzheimer's disease-like pathology and cognitive decline in aged 3xTgAD mice, Am J Pathol, vol.181, issue.2, pp.616-625, 2012.

M. M. Miller-thomas, A. L. Sipe, T. L. Benzinger, J. Mcconathy, S. Connolly et al., , 2016.

, Multimodality Review of Amyloid-related Diseases of the Central Nervous System, Radiographics, vol.36, issue.4, pp.1147-1163

H. J. Moller and M. B. Graeber, The case described by Alois Alzheimer in 1911. Historical and conceptual perspectives based on the clinical record and neurohistological sections, Eur Arch Psychiatry Clin Neurosci, vol.248, issue.3, pp.111-122, 1998.

O. R. Monro, J. B. Mackic, S. Yamada, M. B. Segal, J. Ghiso et al.,

V. Zlokovic, Substitution at codon 22 reduces clearance of Alzheimer's amyloid-beta peptide from the cerebrospinal fluid and prevents its transport from the central nervous system into blood, Neurobiol Aging, vol.23, issue.3, pp.405-412, 2002.

P. Mookherjee, P. S. Green, G. S. Watson, M. A. Marques, K. Tanaka et al., GLT-1 loss accelerates cognitive deficit onset in an Alzheimer's disease animal model, J Alzheimers Dis, vol.26, issue.3, pp.447-455, 2011.

J. A. Morales-garcia, R. Luna-medina, S. Alonso-gil, M. Sanz-sancristobal, V. Palomo et al., Glycogen synthase kinase 3 inhibition promotes adult hippocampal neurogenesis in vitro and in vivo, ACS Chem Neurosci, vol.3, issue.11, pp.963-971, 2012.

R. O. Moreira, S. C. Campos, and A. L. Soldera, Type 2 Diabetes Mellitus and Alzheimer's Disease: from physiopathology to treatment implications, Diabetes Metab Res Rev, 2013.

M. Morris, G. M. Knudsen, and S. Maeda, Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice, vol.18, pp.1183-1189, 2015.

M. Morris, S. Maeda, K. Vossel, and L. Mucke, The many faces of tau, Neuron, vol.70, issue.3, pp.410-426, 2011.

R. G. Morris, Spatial localization does not require the presence of local cues, Learning and Motivation, vol.12, issue.2, pp.239-260, 1981.

A. Mudher, M. Colin, S. Dujardin, M. Medina, I. Dewachter et al.,

L. Mandelkow, M. Buee, J. P. Goedert, and . Brion, What is the evidence that tau pathology spreads through prion-like propagation?, Acta Neuropathol Commun, vol.5, issue.1, p.99, 2017.

E. J. Mufson, S. E. Counts, S. E. Perez, and S. D. Ginsberg, Cholinergic system during the progression of Alzheimer's disease: therapeutic implications, Expert Rev Neurother, vol.8, issue.11, pp.1703-1718, 2008.

M. M. Murray, S. L. Bernstein, V. Nyugen, M. M. Condron, D. B. Teplow et al., Amyloid beta protein: Abeta40 inhibits Abeta42 oligomerization, J Am Chem Soc, vol.131, issue.18, pp.6316-6317, 2009.

E. M. Mutisya, A. C. Bowling, and M. F. Beal, Cortical cytochrome oxidase activity is reduced in Alzheimer's disease, J Neurochem, vol.63, issue.6, pp.2179-2184, 1994.

A. Nabers, J. Ollesch, J. Schartner, C. Kotting, J. Genius et al., Amyloid-beta-Secondary Structure Distribution in Cerebrospinal Fluid and Blood Measured by an Immuno-Infrared-Sensor: A Biomarker Candidate for Alzheimer's Disease, Anal Chem, vol.88, issue.5, pp.2755-2762, 2016.

A. Nabers, L. Perna, J. Lange, U. Mons, J. Schartner et al., Amyloid blood biomarker detects Alzheimer's disease, p.10, 2018.

G. Naert, V. Ferre, J. Meunier, E. Keller, S. Malmstrom et al.,

M. , Leucettine L41, a DYRK1A-preferential DYRKs/CLKs inhibitor, prevents memory impairments and neurotoxicity induced by oligomeric Abeta peptide administration in mice, Eur Neuropsychopharmacol, 2015.

A. Nakamura, N. Kaneko, V. L. Villemagne, T. Kato, J. Doecke et al., High performance plasma amyloid-beta biomarkers for Alzheimer's disease, Nature, vol.554, issue.7691, pp.249-254, 2018.

T. L. Nguyen, C. Fruit, Y. Herault, L. Meijer, and T. Besson, Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) inhibitors: a survey of recent patent literature, Expert Opin Ther Pat, vol.27, issue.11, pp.1183-1199, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02046302

M. Nistor, M. Don, M. Parekh, F. Sarsoza, M. Goodus et al.,

M. Lott, E. Hill, and . Head, Alpha-and beta-secretase activity as a function of age and betaamyloid in Down syndrome and normal brain, Neurobiol Aging, vol.28, issue.10, pp.1493-1506, 2007.

C. M. Norris, I. Kadish, E. M. Blalock, K. C. Chen, V. Thibault et al.,

. Kraner, Calcineurin triggers reactive/inflammatory processes in astrocytes and is upregulated in aging and Alzheimer's models, J Neurosci, vol.25, issue.18, pp.4649-4658, 2005.

S. Oddo, L. Billings, J. P. Kesslak, D. H. Cribbs, and F. M. Laferla, Abeta immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome, Neuron, vol.43, issue.3, pp.321-332, 2004.

S. Oddo, A. Caccamo, K. N. Green, K. Liang, L. Tran et al., Chronic nicotine administration exacerbates tau pathology in a transgenic model of Alzheimer's disease, Proc Natl Acad Sci U S A, vol.102, issue.8, pp.3046-3051, 2005.

S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde et al.,

Y. Mattson, F. M. Akbari, and . Laferla, Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction, Neuron, vol.39, issue.3, pp.409-421, 2003.

S. Oddo, A. Caccamo, L. Tran, M. P. Lambert, C. G. Glabe et al., Temporal profile of amyloid-beta (Abeta) oligomerization in an in vivo model of Alzheimer disease. A link between Abeta and tau pathology, J Biol Chem, vol.281, issue.3, pp.1599-1604, 2006.

Y. Ogawa, Y. Nonaka, T. Goto, E. Ohnishi, T. Hiramatsu et al., Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A, Nat Commun, vol.1, p.86, 2010.

N. Okamura, S. Furumoto, M. T. Fodero-tavoletti, R. S. Mulligan, R. Harada et al., Non-invasive assessment of Alzheimer's disease neurofibrillary pathology using 18F-THK5105 PET, Brain, vol.137, pp.1762-1771, 2014.

M. Okui, T. Ide, K. Morita, E. Funakoshi, F. Ito et al., High-level expression of the Mnb/Dyrk1A gene in brain and heart during rat early development, Genomics, vol.62, issue.2, pp.165-171, 1999.

I. G. Onyango, J. Dennis, and S. M. Khan, Mitochondrial Dysfunction in Alzheimer's Disease and the Rationale for Bioenergetics Based Therapies, Aging Dis, vol.7, issue.2, pp.201-214, 2016.

J. Ortiz-abalia, I. Sahun, X. Altafaj, N. Andreu, X. Estivill et al., Targeting Dyrk1A with AAVshRNA attenuates motor alterations in TgDyrk1A, a mouse model of Down syndrome, Am J Hum Genet, vol.83, issue.4, pp.479-488, 2008.

X. D. Pan, Y. G. Zhu, N. Lin, J. Zhang, Q. Y. Ye et al., Microglial phagocytosis induced by fibrillar beta-amyloid is attenuated by oligomeric beta-amyloid: implications for Alzheimer's disease, Mol Neurodegener, vol.6, p.45, 2011.

J. Park, W. J. Song, and K. C. Chung, Function and regulation of Dyrk1A: towards understanding Down syndrome, Cell Mol Life Sci, vol.66, issue.20, pp.3235-3240, 2009.

M. P. Parsons and L. A. Raymond, Extrasynaptic NMDA receptor involvement in central nervous system disorders, Neuron, vol.82, issue.2, pp.279-293, 2014.

R. L. Patton, W. M. Kalback, C. L. Esh, T. A. Kokjohn, G. D. Van-vickle et al., Amyloid-beta peptide remnants in AN-1792-immunized Alzheimer's disease patients: a biochemical analysis, Am J Pathol, vol.169, issue.3, pp.1048-1063, 2006.

T. Pawson and M. Kofler, Kinome signaling through regulated protein-protein interactions in normal and cancer cells, Curr Opin Cell Biol, vol.21, issue.2, pp.147-153, 2009.

M. Perdomini, B. Belbellaa, L. Monassier, L. Reutenauer, N. Messaddeq et al., Prevention and reversal of severe mitochondrial cardiomyopathy by gene therapy in a mouse model of Friedreich's ataxia, Nat Med, vol.20, issue.5, pp.542-547, 2014.

D. P. Perl, Neuropathology of Alzheimer's disease, Mt Sinai J Med, vol.77, issue.1, pp.32-42, 2010.

M. Phaneuf and M. T. Bal-craquin, La maladie d'Alzheimer et la prise en charge infirmière, 2007.

H. Pilcher, Alzheimer's mouse model raises treatment queries, Lancet Neurol, vol.5, issue.1, p.28, 2006.

A. Pines, Surgical menopause and cognitive decline, Climacteric, vol.17, issue.5, pp.580-582, 2014.

J. Poirier, Apolipoprotein E, cholesterol transport and synthesis in sporadic Alzheimer's disease, Neurobiol Aging, vol.26, issue.3, pp.355-361, 2005.

J. C. Polanco, C. Li, L. G. Bodea, R. Martinez-marmol, F. A. Meunier et al., Amyloid-beta and tau complexity -towards improved biomarkers and targeted therapies, Nat Rev Neurol, vol.14, issue.1, pp.22-39, 2018.

J. C. Polanco, C. Li, N. Durisic, R. Sullivan, and J. Gotz, Exosomes taken up by neurons hijack the endosomal pathway to spread to interconnected neurons, vol.6, p.10, 2018.

M. Polydoro, V. I. Dzhala, A. M. Pooler, S. B. Nicholls, A. P. Mckinney et al., Soluble pathological tau in the entorhinal cortex leads to presynaptic deficits in an early Alzheimer's disease model, Acta Neuropathol, vol.127, issue.2, pp.257-270, 2014.

B. Portha, M. H. Giroix, C. Tourrel-cuzin, H. Le-stunff, and J. Movassat, The GK rat: a prototype for the study of non-overweight type 2 diabetes, Methods Mol Biol, vol.933, pp.125-159, 2012.

B. Potier, J. M. Billard, S. Riviere, P. M. 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, Aging Cell, vol.9, issue.5, pp.722-735, 2010.

S. Prokop, K. R. Miller, and F. L. Heppner, Microglia actions in Alzheimer's disease, Acta Neuropathol, vol.126, issue.4, pp.461-477, 2013.

X. Qian, B. Hamad, and G. Dias-lalcaca, The Alzheimer disease market, Nat Rev Drug Discov, vol.14, issue.10, pp.675-676, 2015.

K. B. Rajan, R. S. Wilson, J. Weuve, L. L. Barnes, and D. A. Evans, Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia, Neurology, vol.85, issue.10, pp.898-904, 2015.

M. Rechsteiner and S. W. Rogers, PEST sequences and regulation by proteolysis, Trends Biochem Sci, vol.21, issue.7, pp.267-271, 1996.

P. Regan and T. Piers, Tau phosphorylation at serine 396 residue is required for hippocampal LTD, vol.35, pp.4804-4812, 2015.

E. D. Roberson, K. Scearce-levie, J. J. Palop, F. Yan, I. H. Cheng et al.,

. Mucke, Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model, Science, vol.316, issue.5825, pp.750-754, 2007.

E. Rogaeva, Y. Meng, J. H. Lee, Y. Gu, T. Kawarai et al.,

D. Petersen, S. D. Dickson, P. E. Der, G. Fraser, S. Schmitt-ulms et al., The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease, Nat Genet, vol.39, issue.2, pp.168-177, 2007.

S. Rogers, R. Wells, and M. Rechsteiner, Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis, Science, vol.234, issue.4774, pp.364-368, 1986.

M. Roy, C. Cardoso, O. Dorieux, C. Malgorn, S. Epelbaum et al., Age-associated evolution of plasmatic amyloid in mouse lemur primates: relationship with intracellular amyloid deposition, Neurobiol Aging, vol.36, issue.1, pp.149-156, 2015.
URL : https://hal.archives-ouvertes.fr/mnhn-02291873

P. Rudrabhatla, H. Jaffe, and H. C. Pant, Direct evidence of phosphorylated neuronal intermediate filament proteins in neurofibrillary tangles (NFTs): phosphoproteomics of Alzheimer's NFTs, Faseb j, vol.25, issue.11, pp.3896-3905, 2011.

N. Ruiz-opazo, K. S. Kosik, L. V. Lopez, P. Bagamasbad, L. R. Ponce et al., Attenuated hippocampus-dependent learning and memory decline in transgenic TgAPPswe Fischer-344 rats, Mol Med, vol.10, issue.1-6, pp.36-44, 2004.

S. R. Ryoo, H. J. Cho, H. W. Lee, H. K. Jeong, C. Radnaabazar et al., Dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A-mediated phosphorylation of amyloid precursor protein: evidence for a functional link between Down syndrome and Alzheimer's disease, J Neurochem, vol.104, issue.5, pp.1333-1344, 2008.

S. R. Ryoo, H. K. Jeong, C. Radnaabazar, J. J. Yoo, and H. J. Cho,

S. H. Ahn, W. J. Chung, and . Song, DYRK1A-mediated hyperphosphorylation of Tau. A functional link between Down syndrome and Alzheimer disease, J Biol Chem, vol.282, issue.48, pp.34850-34857, 2007.

Y. S. Ryu, S. Y. Park, M. S. Jung, S. H. Yoon, M. Y. Kwen et al.,

H. Kim, K. Kim, W. J. Kim, S. H. Song, and . Chung, Dyrk1A-mediated phosphorylation of Presenilin 1: a functional link between Down syndrome and Alzheimer's disease, J Neurochem, vol.115, issue.3, pp.574-584, 2010.

J. J. Sabbagh and C. A. Dickey, The Metamorphic Nature of the Tau Protein: Dynamic Flexibility Comes at a Cost, Front Neurosci, vol.10, p.3, 2016.

C. Sala-frigerio and B. Strooper, Alzheimer's Disease Mechanisms and Emerging Roads to Novel Therapeutics, Annu Rev Neurosci, vol.39, pp.57-79, 2016.

S. Salloway, R. Sperling, and H. R. Brashear, Phase 3 trials of solanezumab and bapineuzumab for Alzheimer's disease, N Engl J Med, vol.370, issue.15, p.1460, 2014.

S. W. Scheff and D. A. Price, Synaptic density in the inner molecular layer of the hippocampal dentate gyrus in Alzheimer disease, J Neuropathol Exp Neurol, vol.57, issue.12, pp.1146-1153, 1998.

P. Scheltens, K. Blennow, M. M. Breteler, B. Strooper, G. B. Frisoni et al., Alzheimer's disease, Lancet, vol.388, pp.505-517, 2016.
URL : https://hal.archives-ouvertes.fr/inserm-01723790

K. Schindowski, A. Bretteville, K. Leroy, S. Begard, J. P. Brion et al., , 2006.

, Alzheimer's disease-like tau neuropathology leads to memory deficits and loss of functional synapses in a novel mutated tau transgenic mouse without any motor deficits, Am J Pathol, vol.169, issue.2, pp.599-616

D. E. Schmechel, A. M. Saunders, W. J. Strittmatter, B. J. Crain, C. M. Hulette et al., Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease, Proc Natl Acad Sci U S A, vol.90, issue.20, pp.9649-9653, 1993.

D. J. Selkoe, Alzheimer's disease. In the beginning, Nature, vol.354, issue.6353, pp.432-433, 1991.

D. J. Selkoe, Alzheimer's disease is a synaptic failure, Science, vol.298, issue.5594, 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, issue.6, pp.595-608, 2016.

L. A. Selznick, D. M. Holtzman, B. H. Han, M. Gokden, A. N. Srinivasan et al., In situ immunodetection of neuronal caspase-3 activation in Alzheimer disease, J Neuropathol Exp Neurol, vol.58, issue.9, pp.1020-1026, 1999.

L. Sereno, M. Coma, M. Rodriguez, P. Sanchez-ferrer, M. B. Sanchez et al., A novel GSK-3beta inhibitor reduces Alzheimer's pathology and rescues neuronal loss in vivo, Neurobiol Dis, vol.35, issue.3, pp.359-367, 2009.

M. Serpente, R. Bonsi, E. Scarpini, and D. Galimberti, Innate immune system and inflammation in Alzheimer's disease: from pathogenesis to treatment, Neuroimmunomodulation, vol.21, issue.2-3, pp.79-87, 2014.

A. Serrano-pozo, M. P. Frosch, E. Masliah, and B. T. Hyman, Neuropathological alterations in Alzheimer disease, Cold Spring Harb Perspect Med, vol.1, issue.1, p.6189, 2011.

R. Sherrington, E. I. Rogaev, Y. Liang, E. A. Rogaeva, G. Levesque et al.,

T. Holman, L. Tsuda, J. F. Mar, A. C. Foncin, M. P. Bruni et al., Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease, Nature, vol.375, issue.6534, pp.754-760, 1995.

Y. Shi, K. Yamada, S. A. Liddelow, S. T. Smith, L. Zhao et al., ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy, Nature, vol.549, issue.7673, pp.523-527, 2017.

R. W. Shin, K. Ogino, A. Shimabuku, T. Taki, H. Nakashima et al., Amyloid precursor protein cytoplasmic domain with phospho-Thr668 accumulates in Alzheimer's disease and its transgenic models: a role to mediate interaction of Abeta and tau, Acta Neuropathol, vol.113, issue.6, pp.627-636, 2007.

K. Shoghi-jadid, G. W. Small, E. D. Agdeppa, V. Kepe, L. M. Ercoli et al., Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease, Am J Geriatr Psychiatry, vol.10, issue.1, pp.24-35, 2002.

S. D. Shumway, M. Maki, and S. Miyamoto, The PEST domain of IkappaBalpha is necessary and sufficient for in vitro degradation by mu-calpain, J Biol Chem, vol.274, issue.43, pp.30874-30881, 1999.

A. R. Simard, D. Soulet, G. Gowing, J. P. Julien, and S. Rivest, Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease, Neuron, vol.49, issue.4, pp.489-502, 2006.

G. Simic, M. Leko, S. Wray, C. Harrington, I. Delalle et al., Tau Protein Hyperphosphorylation and Aggregation in Alzheimer's Disease and Other Tauopathies, and Possible Neuroprotective Strategies, Biomolecules, vol.6, issue.1, p.6, 2016.

A. Singh-manoux, A. Dugravot, A. Fournier, J. Abell, K. Ebmeier et al., Trajectories of Depressive Symptoms Before Diagnosis of Dementia: A 28-Year Follow-up Study, JAMA Psychiatry, vol.74, issue.7, pp.712-718, 2017.

S. A. Small and K. Duff, Linking Abeta and tau in late-onset Alzheimer's disease: a dual pathway hypothesis, Neuron, vol.60, issue.4, pp.534-542, 2008.

B. Smith, F. Medda, V. Gokhale, T. Dunckley, and C. Hulme, Recent advances in the design, synthesis, and biological evaluation of selective DYRK1A inhibitors: a new avenue for a disease modifying treatment of Alzheimer's?, ACS Chem Neurosci, vol.3, issue.11, pp.857-872, 2012.

E. Soeda, D. X. Hou, K. Osoegawa, Y. Atsuchi, T. Yamagata et al., Cosmid assembly and anchoring to human chromosome 21, Genomics, vol.25, issue.1, pp.73-84, 1995.

M. V. Sofroniew, Multiple roles for astrocytes as effectors of cytokines and inflammatory mediators, Neuroscientist, vol.20, issue.2, pp.160-172, 2014.

C. M. Sondag, G. Dhawan, and C. K. Combs, Beta amyloid oligomers and fibrils stimulate differential activation of primary microglia, J Neuroinflammation, vol.6, p.1, 2009.

W. J. Song, S. H. Chung, and D. M. Kurnit, The murine Dyrk protein maps to chromosome 16, localizes to the nucleus, and can form multimers, Biochem Biophys Res Commun, vol.231, issue.3, pp.640-644, 1997.

W. J. Song, L. R. Sternberg, C. Kasten-sportes, M. L. Keuren, S. H. Chung et al.,

P. W. Glover, L. Chiang, D. M. Lou, and . Kurnit, Isolation of human and murine homologues of the Drosophila minibrain gene: human homologue maps to 21q22.2 in the Down syndrome "critical region, Genomics, vol.38, issue.3, pp.331-339, 1996.

B. Souchet, F. Guedj, Z. Penke-verdier, F. Daubigney, A. Duchon et al., Pharmacological correction of excitation/inhibition imbalance in Down syndrome mouse models, Front Behav Neurosci, vol.9, p.267, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01263753

B. Souchet, F. Guedj, I. Sahun, A. Duchon, F. Daubigney et al., , 2014.

, Excitation/inhibition balance and learning are modified by Dyrk1a gene dosage, Neurobiol Dis, vol.69, pp.65-75

B. Souchet, A. M. Billoir, B. Lecanu, L. Tada, S. Braudeau et al., , 2018.

, Alzheimer's disease drug development strategy by targeting its silent phase, NEURAL REGENERATION RESEARCH

R. A. Sperling, P. S. Aisen, L. A. Beckett, D. A. Bennett, S. Craft et al., Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on AgingAlzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease, Alzheimers Dement, vol.7, issue.3, pp.280-292, 2011.

M. G. Spillantini and M. Goedert, Tau pathology and neurodegeneration, Lancet Neurol, vol.12, issue.6, pp.609-622, 2013.

T. L. Spires-jones, K. J. Kopeikina, R. M. Koffie, A. De-calignon, and B. T. Hyman, Are tangles as toxic as they look?, J Mol Neurosci, vol.45, issue.3, pp.438-444, 2011.

T. L. Spires-jones, W. H. Stoothoff, A. De-calignon, P. B. Jones, and B. T. Hyman, Tau pathophysiology in neurodegeneration: a tangled issue, Trends Neurosci, vol.32, issue.3, pp.150-159, 2009.

T. L. Spires, J. D. Orne, K. Santacruz, R. Pitstick, G. A. Carlson et al., Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopathy, Am J Pathol, vol.168, issue.5, pp.1598-1607, 2006.

F. Stagni, A. Giacomini, S. Guidi, E. Ciani, E. Ragazzi et al.,

. Bartesaghi, Long-term effects of neonatal treatment with fluoxetine on cognitive performance in Ts65Dn mice, Neurobiol Dis, vol.74, pp.204-218, 2015.

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, issue.5, pp.1977-1981, 1993.

J. D. Sweatt, Neural plasticity and behavior -sixty years of conceptual advances, J Neurochem, vol.139, pp.179-199, 2016.

T. Tahtouh, J. M. Elkins, P. Filippakopoulos, M. Soundararajan, G. Burgy et al., Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B, J Med Chem, vol.55, issue.21, pp.9312-9330, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00870472

S. Takeda, N. Sato, K. Uchio-yamada, K. Sawada, T. Kunieda et al., Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Abeta deposition in an Alzheimer mouse model with diabetes, Proc Natl Acad Sci U S A, vol.107, issue.15, pp.7036-7041, 2010.

M. Talantova, S. Sanz-blasco, X. Zhang, P. Xia, M. W. Akhtar et al., Abeta induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss, Proc Natl Acad Sci U S A, vol.110, issue.27, pp.2518-2527, 2013.

K. Tanemura, M. Murayama, T. Akagi, T. Hashikawa, T. Tominaga et al., Neurodegeneration with tau accumulation in a transgenic mouse expressing V337M human tau, J Neurosci, vol.22, issue.1, pp.133-141, 2002.

Y. Tang and W. Le, Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases, Mol Neurobiol, vol.53, issue.2, pp.1181-1194, 2016.

R. E. Tanzi and L. Bertram, Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective, Cell, vol.120, issue.4, pp.545-555, 2005.

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, issue.4791, pp.880-884, 1987.

E. Tarkowski, N. Andreasen, A. Tarkowski, and K. Blennow, Intrathecal inflammation precedes development of Alzheimer's disease, J Neurol Neurosurg Psychiatry, vol.74, issue.9, pp.1200-1205, 2003.

J. K. Teller, C. Russo, L. M. Debusk, G. Angelini, D. Zaccheo et al., Presence of soluble amyloid beta-peptide precedes amyloid plaque formation in Down's syndrome, Nat Med, vol.2, issue.1, pp.93-95, 1996.

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, issue.4, pp.572-580, 1991.

D. R. Thal, U. Rub, 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, issue.12, pp.1791-1800, 2002.

T. Tomiyama, S. Matsuyama, H. Iso, T. Umeda, H. Takuma et al., A mouse model of amyloid beta oligomers: their contribution to synaptic alteration, abnormal tau phosphorylation, glial activation, and neuronal loss in vivo, J Neurosci, vol.30, issue.14, pp.4845-4856, 2010.

G. Tosto and C. Reitz, Genome-wide association studies in Alzheimer's disease: a review, Curr Neurol Neurosci Rep, vol.13, issue.10, p.381, 2013.

M. E. Tremblay, B. Stevens, A. Sierra, H. Wake, A. Bessis et al., The role of microglia in the healthy brain, J Neurosci, vol.31, issue.45, pp.16064-16069, 2011.

F. Trinchese, M. Fa, S. Liu, H. Zhang, A. Hidalgo et al.,

R. A. Mathews, O. Nixon, and . Arancio, Inhibition of calpains improves memory and synaptic transmission in a mouse model of Alzheimer disease, J Clin Invest, vol.118, issue.8, pp.2796-2807, 2008.

L. Troquier, R. Caillierez, S. Burnouf, F. J. Fernandez-gomez, M. E. Grosjean et al., Targeting phospho-Ser422 by active Tau Immunotherapy in the THYTau22 mouse model: a suitable therapeutic approach, Curr Alzheimer Res, vol.9, issue.4, pp.397-405, 2012.
URL : https://hal.archives-ouvertes.fr/inserm-00664452

S. L. Tyas, R. B. Tate, K. Wooldrage, J. Manfreda, and L. A. Strain, Estimating the incidence of dementia: the impact of adjusting for subject attrition using health care utilization data, Ann Epidemiol, vol.16, issue.6, pp.477-484, 2006.

J. A. Ubersax, J. E. Ferrell, and J. , Mechanisms of specificity in protein phosphorylation, Nat Rev Mol Cell Biol, vol.8, issue.7, pp.530-541, 2007.

D. Varon, D. A. Loewenstein, E. Potter, M. T. Greig, J. Agron et al., Minimal atrophy of the entorhinal cortex and hippocampus: progression of cognitive impairment, Dement Geriatr Cogn Disord, vol.31, issue.4, pp.276-283, 2011.

J. L. Vazquez-higuera, P. Sanchez-juan, E. Rodriguez-rodriguez, I. Mateo, A. Pozueta et al.,

F. Sastre, J. Valdivieso, M. J. Berciano, O. Bullido, and . Combarros, DYRK1A genetic variants are not linked to Alzheimer's disease in a Spanish case-control cohort, BMC Med Genet, vol.10, p.129, 2009.

V. L. Villemagne, S. Burnham, P. Bourgeat, B. Brown, K. A. Ellis et al., Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study, Lancet Neurol, vol.12, issue.4, pp.357-367, 2013.

K. C. Walls, R. R. Ager, V. Vasilevko, D. Cheng, R. Medeiros et al., p-Tau immunotherapy reduces soluble and insoluble tau in aged 3xTg-AD mice, vol.575, pp.96-100, 2014.

A. Walte, K. Ruben, R. Birner-gruenberger, C. Preisinger, S. Bamberg-lemper et al., Mechanism of dual specificity kinase activity of DYRK1A, Febs j, vol.280, issue.18, pp.4495-4511, 2013.

J. Wan, A. K. Fu, F. C. Ip, H. K. Ng, J. Hugon et al., , 2010.

, /STAT3 signaling mediates beta-amyloid-induced neuronal cell death: implications in Alzheimer's disease, J Neurosci, vol.30, pp.6873-6881

H. Y. Wang, D. H. Lee, M. R. D'andrea, P. A. Peterson, R. P. Shank et al., betaAmyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology, J Biol Chem, vol.275, issue.8, pp.5626-5632, 2000.

Y. Wang, V. Balaji, S. Kaniyappan, L. Kruger, S. Irsen et al., The release and trans-synaptic transmission of Tau via exosomes, Mol Neurodegener, vol.12, issue.1, p.5, 2017.

Y. Wang, M. Cella, K. Mallinson, J. D. Ulrich, K. L. Young et al., TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model, Cell, vol.160, issue.6, pp.1061-1071, 2015.

Z. C. Wang, J. Zhao, and S. Li, Dysregulation of synaptic and extrasynaptic N-methyl-D-aspartate receptors induced by amyloid-beta, Neurosci Bull, vol.29, issue.6, pp.752-760, 2013.

J. Wegiel, K. Dowjat, W. Kaczmarski, I. Kuchna, K. Nowicki et al., The role of overexpressed DYRK1A protein in the early onset of neurofibrillary degeneration in Down syndrome, Acta Neuropathol, vol.116, issue.4, pp.391-407, 2008.

J. Wegiel, C. X. Gong, and Y. W. Hwang, The role of DYRK1A in neurodegenerative diseases, Febs j, vol.278, issue.2, pp.236-245, 2011.

J. Wegiel, W. Kaczmarski, M. Barua, I. Kuchna, K. Nowicki et al., Link between DYRK1A overexpression and several-fold enhancement of neurofibrillary degeneration with 3-repeat tau protein in Down syndrome, J Neuropathol Exp Neurol, vol.70, issue.1, pp.36-50, 2011.

J. Wegiel, I. Kuchna, K. Nowicki, J. Frackowiak, K. Dowjat et al., Cell type-and brain structurespecific patterns of distribution of minibrain kinase in human brain, Brain Res, vol.1010, issue.1-2, pp.69-80, 2004.

J. Wegiel, K. C. Wang, H. Imaki, R. Rubenstein, A. Wronska et al., The role of microglial cells and astrocytes in fibrillar plaque evolution in transgenic APP(SW) mice, Neurobiol Aging, vol.22, issue.1, pp.49-61, 2001.

M. D. Weingarten, A. H. Lockwood, S. Y. Hwo, and M. W. Kirschner, A protein factor essential for microtubule assembly, Proc Natl Acad Sci U S A, vol.72, issue.5, pp.1858-1862, 1975.

R. O. Weller, D. Boche, and J. A. Nicoll, Microvasculature changes and cerebral amyloid angiopathy in Alzheimer's disease and their potential impact on therapy, Acta Neuropathol, vol.118, issue.1, pp.87-102, 2009.

R. O. Weller and J. A. Nicoll, Cerebral amyloid angiopathy: pathogenesis and effects on the ageing and Alzheimer brain, Neurol Res, vol.25, issue.6, pp.611-616, 2003.

J. L. Wemeau and M. Ladsous, )): The teachings of a senseless polemic, Presse Med, vol.46, issue.10, pp.887-889, 2017.

P. S. Weston, J. M. Nicholas, S. M. Henley, Y. Liang, K. Macpherson et al., Accelerated long-term forgetting in presymptomatic autosomal dominant Alzheimer's disease: a cross-sectional study, Lancet Neurol, vol.17, issue.2, pp.123-132, 2018.

S. Wiechmann, H. Czajkowska, K. De-graaf, J. Grotzinger, H. G. Joost et al., Unusual function of the activation loop in the protein kinase DYRK1A, Biochem Biophys Res Commun, vol.302, issue.2, pp.403-408, 2003.

J. Wiltfang, H. Esselmann, M. Bibl, M. Hull, H. Hampel et al., Amyloid beta peptide ratio 42/40 but not A beta 42 correlates with phospho-Tau in patients with low-and high-CSF A beta 40 load, J Neurochem, vol.101, issue.4, pp.1053-1059, 2007.

H. M. Wisniewski and A. Rabe, Discrepancy between Alzheimer-type neuropathology and dementia in persons with Down's syndrome, Ann N Y Acad Sci, vol.477, pp.247-260, 1986.

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, issue.3, pp.278-282, 1985.

C. W. Wittmann, M. F. Wszolek, J. M. Shulman, P. M. Salvaterra, J. Lewis et al., Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles, Science, vol.293, issue.5530, pp.711-714, 2001.

G. Wolber, T. Seidel, F. Bendix, and T. Langer, Molecule-pharmacophore superpositioning and pattern matching in computational drug design, Drug Discov Today, vol.13, issue.1-2, pp.23-29, 2008.

Y. L. Woods, P. Cohen, W. Becker, R. Jakes, M. Goedert et al., The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bepsilon at Ser539 and the microtubuleassociated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase, Biochem J, vol.355, pp.609-615, 2001.

P. Wu, T. E. Nielsen, and M. H. Clausen, FDA-approved small-molecule kinase inhibitors, Trends Pharmacol Sci, vol.36, issue.7, pp.422-439, 2015.

P. Wu, T. E. Nielsen, and M. H. Clausen, Small-molecule kinase inhibitors: an analysis of FDAapproved drugs, Drug Discov Today, vol.21, issue.1, pp.5-10, 2016.

Q. S. Xue and W. J. Streit, Microglial pathology in Down syndrome, Acta Neuropathol, vol.122, issue.4, pp.455-466, 2011.

P. Yaish, A. Gazit, C. Gilon, and A. Levitzki, Blocking of EGF-dependent cell proliferation by EGF receptor kinase inhibitors, Science, vol.242, issue.4880, pp.933-935, 1988.

M. Yamada, Cerebral amyloid angiopathy: emerging concepts, J Stroke, vol.17, issue.1, pp.17-30, 2015.

S. S. Yoon and S. A. Jo, Mechanisms of Amyloid-beta Peptide Clearance: Potential Therapeutic Targets for Alzheimer's Disease, Biomol Ther (Seoul), vol.20, issue.3, pp.245-255, 2012.

T. Yoon, J. Okada, M. W. Jung, and J. J. Kim, Prefrontal cortex and hippocampus subserve different components of working memory in rats, Learn Mem, vol.15, issue.3, pp.97-105, 2008.

Y. Yoshiyama, M. Higuchi, B. Zhang, S. M. Huang, N. Iwata et al., Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model, Neuron, vol.53, issue.3, pp.337-351, 2007.

C. V. Zerbinatti, S. E. Wahrle, H. Kim, J. A. Cam, K. Bales et al., , 2006.

, Apolipoprotein E and low density lipoprotein receptor-related protein facilitate intraneuronal Abeta42 accumulation in amyloid model mice, J Biol Chem, vol.281, issue.47, pp.36180-36186

Y. Zhao, X. Wu, X. Li, L. L. Jiang, X. Gui et al., TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function, Neuron, vol.97, issue.5, pp.1023-1031, 1027.

J. Zheng, E. A. Trafny, D. R. Knighton, N. H. Xuong, S. S. Taylor et al., 2.2 A refined crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MnATP and a peptide inhibitor, Acta Crystallogr D Biol Crystallogr, vol.49, pp.362-365, 1993.
URL : https://hal.archives-ouvertes.fr/hal-00126646

G. Zhu, Y. Liu, and S. Shaw, Protein kinase specificity. A strategic collaboration between kinase peptide specificity and substrate recruitment, Cell Cycle, vol.4, issue.1, pp.52-56, 2005.

Y. Zou, S. Lim, K. Lee, X. Deng, and E. Friedman, Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell migration and is negatively regulated by the Met adaptor Ran-binding protein M, J Biol Chem, vol.278, issue.49, pp.49573-49581, 2003.