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Vers un marqueur biochimique des dégénérescences lobaires fronto-temporales : variations quantitatives et profils protéiques de la protéine TDP43 dans différentes matrices biologiques

Abstract : Frontotemporal lobar degeneration (FTLD) syndrome is the second most common of presenile dementia. FTLD is a clinically heterogeneous syndrome and comprises many hereditary cases. Common neuropathological features rely on a degeneration of the frontal and/or anterior temporal lobes, associated to specific inclusions of aggregated proteins including TAR DNA binding protein 43 (TDP43). Unfortunately, no practical protein marker is currently validated to improve FTLD diagnosis in living patients.A cohort of FTLD patients with definite TDP43 pathology was defined with the development of specific genetic testing. An analysis of TDP43 concentrations in cerebrospinal fluid (CSF) was performed in this cohort and then compared to other cohorts well-characterized on clinical and neuropathological features. Finally, qualitative patterns of TDP43 were studied in compartments accessible from the patient’s living: profiles of soluble TDP43 protein (in CSF or in plasma) and intracellular TDP43 protein (in the formed elements of blood) were compared to protein patterns observed in brain tissues with TDP43 protein inclusions. Platelet samples exhibit similar characteristics to brain tissue and could become a candidate biomarker for FTLD probabilistic diagnosis
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Anthony Fourier. Vers un marqueur biochimique des dégénérescences lobaires fronto-temporales : variations quantitatives et profils protéiques de la protéine TDP43 dans différentes matrices biologiques. Neurosciences. Université de Lyon, 2018. Français. ⟨NNT : 2018LYSE1269⟩. ⟨tel-02057585⟩

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