8BGS

Tau Paired Helical Filament from Extracellular Vesicles from Alzheimer's disease brain

8BGS の概要

• エントリーDOI: 10.2210/pdb8bgs/pdb
• EMDBエントリー: 16035
• 分子名称: Microtubule-associated protein tau (1 entity in total)
• 機能のキーワード: protein fibril, amyloid
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 321439.10

構造登録者

Behr, T.S.,Ryskeldi-Falcon, B. (登録日: 2022-10-28, 公開日: 2023-05-24, 最終更新日: 2025-03-05)

主引用文献

Fowler, S.L.,Behr, T.S.,Turkes, E.,Cauhy, P.M.,Foiani, M.S.,Schaler, A.,Crowley, G.,Bez, S.,Ficulle, E.,Tsefou, E.,O'Brien, D.P.,Fischer, R.,Geary, B.,Gaur, P.,Miller, C.,D'Acunzo, P.,Levy, E.,Duff, K.E.,Ryskeldi-Falcon, B.
Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease.
Biorxiv, 2023

PubMed Abstract: The abnormal assembly of tau protein in neurons is the pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). In addition, assembled tau associates with extracellular vesicles (EVs) in the central nervous system of patients with AD, which is linked to its clearance and prion-like propagation between neurons. However, the identities of the assembled tau species and the EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from AD patients. We found filaments of truncated tau enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD.

PubMed: 37163117
DOI: 10.1101/2023.04.30.537820

実験手法

ELECTRON MICROSCOPY (3.16 Å)