Evidence map›Paper›PMID 37393617›Full record

ArticleCell reports2023

Super-resolution imaging unveils the self-replication of tau aggregates upon seeding.

Eleni Dimou, Taxiarchis Katsinelos, Georg Meisl, Benjamin J Tuck, Sophie Keeling, Annabel E Smith, Eric Hidari, Jeff Y L Lam, Melanie Burke, Sofia Lövestam and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
12.9field-weighted citation impact, top 1% 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

17 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. A novelAutophagy · 2025
    Article
  6. Beyond prion-like spreading in neurodegenerative disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  7. Review
  8. Small-diffusible aggregates, plaques, tangles, and dynamic equilibria: Untangling Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Precision proteoform design for 4R tau isoform selective templated aggregation.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  16. Article
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Eleni DimouDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK; UK Dementia Research Institute at University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge CB2 0AH, UK. Electronic address: ed538@cam.ac.uk.
Taxiarchis KatsinelosUK Dementia Research Institute at University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge CB2 0AH, UK; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Georg MeislDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
Benjamin J TuckUK Dementia Research Institute at University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge CB2 0AH, UK.
Sophie KeelingUK Dementia Research Institute at University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge CB2 0AH, UK.
Annabel E SmithUK Dementia Research Institute at University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge CB2 0AH, UK.
Eric HidariDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK; UK Dementia Research Institute at University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge CB2 0AH, UK.
Jeff Y L LamDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK; UK Dementia Research Institute at University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge CB2 0AH, UK.
Melanie BurkeDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK; UK Dementia Research Institute at University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge CB2 0AH, UK.
Sofia LövestamMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Rohan T RanasingheDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK; UK Dementia Research Institute at University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge CB2 0AH, UK.
William A McEwanUK Dementia Research Institute at University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge CB2 0AH, UK.
David KlenermanDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK; UK Dementia Research Institute at University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge CB2 0AH, UK. Electronic address: dk10012@cam.ac.uk.
University of Cambridge · GBMRC Laboratory of Molecular Biology · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

Tau is a soluble protein interacting with tubulin to stabilize microtubules. However, under pathological conditions, it becomes hyperphosphorylated and aggregates, a process that can be induced by treating cells with exogenously added tau fibrils. Here, we employ single-molecule localization microscopy to resolve the aggregate species formed in early stages of seeded tau aggregation. We report that entry of sufficient tau assemblies into the cytosol induces the self-replication of small tau aggregates, with a doubling time of 5 h inside HEK cells and 1 day in murine primary neurons, which then grow into fibrils. Seeding occurs in the vicinity of the microtubule cytoskeleton, is accelerated by the proteasome, and results in release of small assemblies into the media. In the absence of seeding, cells still spontaneously form small aggregates at lower levels. Overall, our work provides a quantitative picture of the early stages of templated seeded tau aggregation in cells.

Indexed as

Alzheimer Diseasetau ProteinsAnimalsCytosolMiceMicrotubulesNeuronsProtein AggregatesTubulinProtein Aggregatestau ProteinsTubulinAlzheimer’s diseaseCP: Cell biologyneurodegenerationprotein aggregationseeded aggregationsuper-resolution microscopytau

Identifiers

PMID37393617
PMCPMC7614924
OpenAlexW4382793935

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.