Evidence map›Paper›PMID 25261551›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Proteopathic tau seeding predicts tauopathy in vivo.

Brandon B Holmes, Jennifer L Furman, Thomas E Mahan, Tritia R Yamasaki, Hilda Mirbaha, William C Eades, Larisa Belaygorod, Nigel J Cairns, David M Holtzman, Marc I Diamond

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 452 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
452citing papers in PubMed, 2 pooled it
14.9field-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

452 citing papers in PubMed, 2 syntheses or guidelines pooled it, 731 citations in OpenAlex.

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  18. ThebioRxiv : the preprint server for biology · 2026
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392 more citing papers are in PubMed but not listed here.

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

10 authors at 2 institutions in 1 country.

Brandon B HolmesDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, and.
Jennifer L FurmanDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, and.
Thomas E MahanDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, and.
Tritia R YamasakiDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, and.
Hilda MirbahaDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, and.
William C EadesDivision of Oncology, Section of Stem Cell Biology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Larisa BelaygorodDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, and.
Nigel J CairnsDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, and.
David M HoltzmanDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, and.
Marc I DiamondDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, and marc.diamond@utsouthwestern.edu.
Hope Center for Neurological Disorders · USWashington University in St. Louis · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS, Suzanne Elizabeth Schindler · 1985 to 2026
$69.5M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1M
Washington University Center for Translational NeuroscienceP30NS057105 · NINDS · WASHINGTON UNIVERSITY · PI HOLTZMAN, DAVID M. · 2006 to 2011
$8.7M
CELL-CELL TRANSFER AND PROPAGATION OF TAU AGGREGATESR01NS071835 · NINDS · WASHINGTON UNIVERSITY · PI DIAMOND, MARC I · 2010 to 2014
$1.6M
Screening and Immunization: A Novel Approach to Tau Antibody TherapeuticsF32NS087805 · NINDS · WASHINGTON UNIVERSITY · PI FURMAN, JENNIFER · 2014 to 2016
$145k
Tracking the Propagation of Misfolded Tau: A Study of Cellular Uptake and TrafficF31NS079039 · NINDS · WASHINGTON UNIVERSITY · PI HOLMES, BRANDON BLAKE · 2012 to 2014
$83k
NCI NIH HHS P30 CA091842NCRR NIH HHS S10 RR0227552NIA NIH HHS P01 AG003991NIA NIH HHS P50 AG005681NIA NIH HHS P50AG05681NINDS NIH HHS 1F31NS079039NINDS NIH HHS 1F32NS087805NINDS NIH HHS 1R01NS071835NINDS NIH HHS F31 NS079039NINDS NIH HHS F32 NS087805NINDS NIH HHS NS057105NINDS NIH HHS P30 NS057105NINDS NIH HHS R01 NS071835
6 · The paper itself

Abstract

Transcellular propagation of protein aggregates, or proteopathic seeds, may drive the progression of neurodegenerative diseases in a prion-like manner. In tauopathies such as Alzheimer's disease, this model predicts that tau seeds propagate pathology through the brain via cell-cell transfer in neural networks. The critical role of tau seeding activity is untested, however. It is unknown whether seeding anticipates and correlates with subsequent development of pathology as predicted for a causal agent. One major limitation has been the lack of a robust assay to measure proteopathic seeding activity in biological specimens. We engineered an ultrasensitive, specific, and facile FRET-based flow cytometry biosensor assay based on expression of tau or synuclein fusions to CFP and YFP, and confirmed its sensitivity and specificity to tau (∼ 300 fM) and synuclein (∼ 300 pM) fibrils. This assay readily discriminates Alzheimer's disease vs. Huntington's disease and aged control brains. We then carried out a detailed time-course study in P301S tauopathy mice, comparing seeding activity versus histological markers of tau pathology, including MC1, AT8, PG5, and Thioflavin S. We detected robust seeding activity at 1.5 mo, >1 mo before the earliest histopathological stain. Proteopathic tau seeding is thus an early and robust marker of tauopathy, suggesting a proximal role for tau seeds in neurodegeneration.

Indexed as

AgingAlzheimer DiseaseAnimalsBiomarkersBiosensing TechniquesCells, CulturedDisease Models, AnimalFlow CytometryFluorescence Resonance Energy TransferHEK293 CellsHumansMice, TransgenicMutant ProteinsProtein Aggregation, PathologicalProtein BindingTauopathiesBiomarkersMutant Proteinstau Proteinsagingamyloiddementianeuropathology

Identifiers

PMID25261551
PMCPMC4205609
OpenAlexW1966312717

What OpenQuestion holds

Textmetadata
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.