Univ. Lille, Inserm, CHU-Lille
Alzheimer&Tauopathies, Lille Neuroscience & Cognition

Presenter Of 1 Presentation

EXTRACELLULAR VESICLES: MAJOR ACTORS OF HETEROGENEITY IN TAU SPREADING AMONG HUMAN TAUOPATHIES

Session Type
SYMPOSIUM
Date
Fri, 18.03.2022
Session Time
02:45 PM - 04:45 PM
Room
Onsite: 114
Lecture Time
04:00 PM - 04:15 PM

Abstract

Aims

In somes tauopathies, the progression of neurodegeneration follows disease-specific hierarchical progression that may be linked to a prion-like propagation. Indeed, seed-competent tau species spread from cell to cell but the intercellular mechanisms of transfer are unclear. Extracellular vesicles represent a unique intercellular delivery vehicle for transferring pathological species from one neuronal population to another that could explain the differing cell vulnerability seen in tauopathies. Here, we compare tau seeding capacity from vesicles that have been isolated from brain derived fluid of patients with various tauopathies.

Methods

Brain extracts (AD, PSP, PiD, control) were obtained from the Lille Neurobank. Vesicles were characterized (electron microscopy, nanotracking analyses, mass spectrometry, biochemistry). Tau in brain-derived enriched-extracellular vesicles (BD-EVs) was evaluated by ELISA and EM. Seeding mediated by BD-EVs was tested using a cell seeding assay; BD-EVs were injected into the hippocampus of tau transgenic mice and tau lesions quantified (MC1 and AT100).

Results

Whereas vesicles concentration and the tau content did not differ among the tauopathies and controls, we observed considerable heterogeneity in their seeding capacities. The most striking evidence was coming from AD where the BD-EVs clearly contain pathological species that can induce tau lesions in vivo. For PSP and PiD patients, a weak FRET signal was observed which was consistent with neuropathology.

Conclusions

Together, our results support the hypothesis that BD-EVs contain tau variants that may participate to the prion-like propagation of tau pathology in tauopathies. Such observation may lead to reconsider diagnostic and therapeutic strategies.

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