Cited by 165Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Extracellular Monomeric Tau Protein Is Sufficient to Initiate the Spread of Tau Protein Pathology

Open access
Michel, Claire H., Kumar, Satish, Pinotsi, Dorothea, Tunnacliffe, Alan, St. George-Hyslop, Peter, Mandelkow, Eckhard, Mandelkow, Eva-Maria, Kaminski, Clemens F. +1 more·2014·Journal of Biological Chemistry

Abstract

Understanding the formation and propagation of aggregates of the Alzheimer disease-associated Tau protein in vivo is vital for the development of therapeutics for this devastating disorder. Using our recently developed live-cell aggregation sensor in neuron-like cells, we demonstrate that different variants of exogenous monomeric Tau, namely full-length Tau (hTau40) and the Tau-derived construct K18 comprising the repeat domain, initially accumulate in endosomal compartments, where they form fibrillar seeds that subsequently induce the aggregation of endogenous Tau. Using superresolution imaging, we confirm that fibrils consisting of endogenous and exogenous Tau are released from cells and demonstrate their potential to spread Tau pathology. Our data indicate a greater pathological risk and potential toxicity than hitherto suspected for extracellular soluble Tau.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1074/jbc.m113.515445

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Michel, C. H., Kumar, S., Pinotsi, D., Tunnacliffe, A., St. George-Hyslop, P., Mandelkow, E., Mandelkow, E.-M., Kaminski, C. F., & Kaminski Schierle, G. S.
Affiliations
  • University of Cambridge (GB)
  • German Center for Neurodegenerative Diseases (DE)
  • Center of Advanced European Studies and Research (DE)
Corresponding author
Kaminski, Clemens F.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2014-01
Volume
289
Issue
2
Pages
956-967
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2151048581
Cited by
165
References
42
Citations by year
2026: 8 · 2025: 11 · 2024: 6 · 2023: 9 · 2022: 10 · 2021: 12 · 2020: 17 · 2019: 15 · 2018: 17 · 2017: 9 · 2016: 21 · 2015: 16 · 2014: 11 · 2013: 2 · 2012: 1
FWCI
12.63
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Max Planck Digital Library (submittedVersion)
  • DZNE Pub (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • Wellcome Trust (089703/Z/09/Z, 100140, 089703, 081864)
  • Medical Research Council (MR/K015850/1, MR/K02292X/1, MC_G1000734)
  • Engineering and Physical Sciences Research Council (EP/H018301/1)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
tau protein, tau aggregation, Alzheimer's disease, endosomes, tau repeat domain, super-resolution imaging
MeSH terms
Animals, Cell Line, Endocytosis, Exocytosis, Extracellular Space, Humans, Lysosomes, Microscopy, Electron, Models, Biological, Neurons, Endosomes, Blotting, Western, Neurofibrillary Tangles, tau Proteins, Microscopy, Confocal, Transport Vesicles, Tauopathies, Cell Line, Tumor

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review