Protein fingerprints of brain-derived extracellular vesicles predict types of tau pathology.

StudyAlzheimer's research & therapy· Oct 2025

Protein fingerprints of brain-derived extracellular vesicles predict types of tau pathology.

Jeanne Espourteille, Aatmika Barve, Valentin Zufferey … Kevin Richetin

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NeuropathologyStudyQ1IF 7.8

Combined glial protein levels perfectly classify Pick's disease, PSP, and controls

Protein fingerprints of brain-derived extracellular vesicles predict types of tau pathology.

Jeanne Espourteille … Kevin Richetin

Alzheimer's research & therapy · Oct 2025

Background

Tauopathies are a heterogeneous group of neurodegenerative disorders characterized by the brain-regional aggregation of three-repeat (3R) or four-repeat (4R) tau isoforms.

Purpose

To determine whether proteomic fingerprints of brain‑derived extracellular vesicles (BD‑EVs) isolated from the prefrontal cortex can (i) distinguish 3R from 4R tauopathies and (ii) mirror the histopathological burden of phosphorylated tau.

Methods

BD‑EVs were purified from post‑mortem prefrontal cortex interstitial fluid of Pick’s disease (PiD; 3R), progressive supranuclear palsy (PSP; 4R), and control cases (CTRL).

F1 = 1.0

Results

F1 = 1.0

glial protein levels alone perfectly separated all three groups

More results

Tau pathology did not alter overall BD‑EV yield but shifted vesicle size distribution in PiD (higher small/large EV ratio).

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Conclusion · 1 of 2

BD‑EV proteomic fingerprints robustly differentiate 3R and 4R tauopathies and track disease severity, unveiling astrocytic mitochondrial proteins as candidate biomarkers.

Conclusion · 2 of 2

Overall, our results indicate that BD-EV profiling may complement existing approaches for distinguishing tau isoforms and, pending further validation, could ultimately be adapted for use in more accessible biofluids.

Protein fingerprints of brain-derived extracellular vesicles predict types of tau pathology.

Protein fingerprints of brain-derived extracellular vesicles predict types of tau pathology.

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