Evidence map›Paper›PMID 35508140›Full record

ArticleCell reports2022

Cholesterol determines the cytosolic entry and seeded aggregation of tau.

Benjamin J Tuck, Lauren V C Miller, Taxiarchis Katsinelos, Annabel E Smith, Emma L Wilson, Sophie Keeling, Shi Cheng, Marina J Vaysburd, Claire Knox, Lucy Tredgett and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
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

34 citing papers in PubMed, 52 citations in OpenAlex.

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  13. The interaction between dysfunction of vasculature and tauopathy in Alzheimer's disease and related dementias.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  14. Unifying biology of neurodegeneration in lysosomal storage diseases.Journal of inherited metabolic disease · 2025
    Review
  15. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Benjamin J TuckUK Dementia Research Institute at the University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge, CB2 0AH, UK. Electronic address: bjt44@cam.ac.uk.
Lauren V C MillerUK Dementia Research Institute at the University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge, CB2 0AH, UK.
Taxiarchis KatsinelosUK Dementia Research Institute at the University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge, CB2 0AH, UK.
Annabel E SmithUK Dementia Research Institute at the University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge, CB2 0AH, UK.
Emma L WilsonUK Dementia Research Institute at the University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge, CB2 0AH, UK.
Sophie KeelingUK Dementia Research Institute at the University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge, CB2 0AH, UK.
Shi ChengUK Dementia Research Institute at the University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge, CB2 0AH, UK.
Marina J VaysburdMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Claire KnoxMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Lucy TredgettMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Emmanouil MetzakopianUK Dementia Research Institute at the University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge, CB2 0AH, UK.
Leo C JamesMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
William A McEwanUK Dementia Research Institute at the University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge, CB2 0AH, UK. Electronic address: wm305@cam.ac.uk.
University of Cambridge · GBMRC Laboratory of Molecular Biology · GBUK Dementia Research Institute · GB

Funding

Medical Research Council MC_U105181010Medical Research Council MC_U105184326Wellcome TrustWellcome Trust 206248/Z/17/Z
6 · The paper itself

Abstract

Assemblies of tau can transit between neurons, seeding aggregation in a prion-like manner. To accomplish this, tau must cross cell-limiting membranes, a process that is poorly understood. Here, we establish assays for the study of tau entry into the cytosol as a phenomenon distinct from uptake, in real time, and at physiological concentrations. The entry pathway of tau is cell type specific and, in neurons, highly sensitive to cholesterol. Depletion of the cholesterol transporter Niemann-Pick type C1 or extraction of membrane cholesterol renders neurons highly permissive to tau entry and potentiates seeding even at low levels of exogenous tau assemblies. Conversely, cholesterol supplementation reduces entry and almost completely blocks seeded aggregation. Our findings establish entry as a rate-limiting step to seeded aggregation and demonstrate that dysregulated cholesterol, a feature of several neurodegenerative diseases, potentiates tau aggregation by promoting entry of tau assemblies into the cell interior.

Indexed as

Alzheimer DiseasePrionsCholesterolCytosolHumansNeuronstau ProteinsCholesterolPrionstau ProteinsAlzheimer’s diseasecholesterolCP: MetabolismCP: NeuroscienceendocytosisneurodegenerationNiemann-Pick diseaseseeded aggregationtau

Identifiers

PMID35508140
PMCPMC9108550
OpenAlexW4229034810

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.