Evidence map›Paper›PMID 39572740›Full record

ArticleNature neuroscience2025

Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease.

Stephanie L Fowler, Tiana S Behr, Emir Turkes, Darragh P O'Brien, Paula Maglio Cauhy, Isadora Rawlinson, Marisa Edmonds, Martha S Foiani, Ari Schaler, Gerard Crowley and 11 more

Abstract read
In one paragraph

Article in Nature neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  8. Article
  9. Article
  10. Article
  11. Review
  12. Emerging directions in tauopathy research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
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  14. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Stephanie L Fowler *UK Dementia Research Institute at University College London, London, UK.ORCID http://orcid.org/0000-0001-6693-9959
Tiana S Behr *Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Emir TurkesUK Dementia Research Institute at University College London, London, UK.
Darragh P O'BrienTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-4924-7795
Paula Maglio CauhyUK Dementia Research Institute at University College London, London, UK.
Isadora RawlinsonMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Marisa EdmondsUK Dementia Research Institute at University College London, London, UK.
Martha S FoianiUK Dementia Research Institute at University College London, London, UK.ORCID http://orcid.org/0000-0003-4157-2606
Ari SchalerTaub Institute, Irving Medical Center, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0003-2504-220X
Gerard CrowleyUK Dementia Research Institute at University College London, London, UK.ORCID http://orcid.org/0000-0003-0436-1332
Sumi BezUK Dementia Research Institute at University College London, London, UK.ORCID http://orcid.org/0000-0002-8971-5103
Elena FiculleUK Dementia Research Institute at University College London, London, UK.
Eliona TsefouUK Dementia Research Institute at University College London, London, UK.
Roman FischerTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-9715-5951
Beth GearyMedical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.
Pallavi GaurDepartment of Neurology, Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-0286-1950
Chelsea MillerThe Center for Genetic and Genomic Medicine, Hackensack University Medical Center, Hackensack, NJ, USA.
Pasquale D'AcunzoCenter for Dementia Research, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.ORCID http://orcid.org/0000-0001-7237-0076
Efrat LevyCenter for Dementia Research, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.ORCID http://orcid.org/0000-0001-6890-6763
Karen E DuffUK Dementia Research Institute at University College London, London, UK. k.duff@ucl.ac.uk.ORCID http://orcid.org/0000-0002-6177-868X
Benjamin Ryskeldi-FalconMedical Research Council Laboratory of Molecular Biology, Cambridge, UK. bfalcon@mrc-lmb.cam.ac.uk.ORCID http://orcid.org/0000-0002-8176-2618

Funding

Uncovering Alzheimer's disease risk mechanisms through neuron-specific analysis of autophagy and endosomal-lysosomal functionP01AG017617 · NIA · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · PI NIXON, RALPH A. · 2000 to 2021
$40.0M
Tauopathy in AD and FTD - Molecular Determinants of Phenotypic DiversityRF1AG056151 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CARLSON, GEORGE A., DUFF, KAREN · 2017 to 2017
$4.1M
Neuronal Protective Apolipoprotein E2-mediated endocytic and exocytic pathwaysRF1AG057517 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI LEVY, EFRAT, MATHEWS, PAUL M · 2017 to 2020
$2.4M
Differential vulnerability to tauopathy in Alzheimer's disease and Frontotemporal Lobe DementiaRF1AG063521 · NIA · UNIVERSITY COLLEGE LONDON · PI DUFF, KAREN · 2019 to 2019
$2.1M
Preventing early events in Aβ-driven pathology in vivoR01AG056732 · NIA · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · PI LEVY, EFRAT · 2017 to 2021
$2.0M
Alzheimer's Association AARF-22-923826Alzheimer's Research UK (ARUK) ARUK-RS2019-001BrightFocus Foundation (BrightFocus) A2017393SNIA NIH HHS P01 AG017617NIA NIH HHS R01 AG056732NIA NIH HHS RF1 AG056151NIA NIH HHS RF1 AG057517NIA NIH HHS RF1 AG063521RCUK | Medical Research Council (MRC) (MC_UP_1201/25U.S. Department of Health & Human Services | National Institutes of Health (NIH) AG017617U.S. Department of Health & Human Services | National Institutes of Health (NIH) AG056151U.S. Department of Health & Human Services | National Institutes of Health (NIH) AG056732U.S. Department of Health & Human Services | National Institutes of Health (NIH) AG063521
6 · The paper itself

Abstract

The abnormal assembly of tau protein in neurons is a pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). Assembled tau associates with extracellular vesicles (EVs) in the central nervous system of individuals with AD, which is linked to its clearance and prion-like propagation. However, the identities of the assembled tau species and 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 individuals with AD. We found tau filaments composed mainly of truncated tau that were 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.

Indexed as

Alzheimer DiseaseBrainExtracellular Vesiclestau ProteinsAgedAged, 80 and overCryoelectron MicroscopyFemaleHumansMaleMAPT protein, humantau Proteins

Identifiers

PMID39572740
PMCPMC11706778

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.