Evidence map›Paper›PMID 33927414›Full record

ArticleNature medicine2021

Four distinct trajectories of tau deposition identified in Alzheimer's disease.

Jacob W Vogel, Alexandra L Young, Neil P Oxtoby, Ruben Smith, Rik Ossenkoppele, Olof T Strandberg, Renaud La Joie, Leon M Aksman, Michel J Grothe, Yasser Iturria-Medina and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 513 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
513citing papers in PubMed, 8 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

513 citing papers in PubMed, 8 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Clinical criteria for limbic-predominant age-related TDP-43 encephalopathy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Pooled it
  8. Pooled it
  9. Trial
  10. Article
  11. Article
  12. Observational
  13. Article
  14. Article
  15. [European journal of nuclear medicine and molecular imaging · 2026
    Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review

453 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

18 authors.

Jacob W VogelMontreal Neurological Institute, McGill University, Montréal, Quebec, Canada. jacob.vogel@mail.mcgill.ca.ORCID http://orcid.org/0000-0001-6394-9940
Alexandra L YoungDepartment of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Neil P OxtobyCentre for Medical Image Computing, University College London, London, UK.ORCID http://orcid.org/0000-0003-0203-3909
Ruben SmithClinical Memory Research Unit, Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0001-7147-0112
Rik OssenkoppeleClinical Memory Research Unit, Lund University, Lund, Sweden.
Olof T StrandbergClinical Memory Research Unit, Lund University, Lund, Sweden.
Renaud La JoieMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-2581-8100
Leon M AksmanCentre for Medical Image Computing, University College London, London, UK.
Michel J GrotheWallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.ORCID http://orcid.org/0000-0003-2600-9022
Yasser Iturria-MedinaMontreal Neurological Institute, McGill University, Montréal, Quebec, Canada.ORCID http://orcid.org/0000-0002-9345-0347
Alzheimer’s Disease Neuroimaging Initiative
Michael J PontecorvoAVID Radiopharmaceuticals, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-8419-7589
Michael D DevousAVID Radiopharmaceuticals, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-6871-0063
Gil D RabinoviciMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-3626-4265
Daniel C AlexanderCentre for Medical Image Computing, University College London, London, UK.ORCID http://orcid.org/0000-0003-2439-350X
Chul Hyoung LyooDepartments of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0003-2231-672X
Alan C EvansMontreal Neurological Institute, McGill University, Montréal, Quebec, Canada.ORCID http://orcid.org/0000-0003-3841-6098
Oskar HanssonClinical Memory Research Unit, Lund University, Lund, Sweden. oskar.hansson@med.lu.se.ORCID http://orcid.org/0000-0001-8467-7286

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
PrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MILLER, BRUCE L · 2004 to 2018
$27.1M
SCHIZOPHRENIA: A NEUROPSYCHIATRIC PERSPECTIVET32MH019112 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GUR, RAQUEL E · 1990 to 2024
$6.2M
Early Age-of-Onset AD: Clinical Heterogeneity and Network DegenerationR01AG045611 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RABINOVICI, GIL DAN · 2014 to 2018
$3.1M
Connectome-based spread of neurodegenerative processes in Alzheimer's diseaseK99AG065501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LA JOIE, RENAUD CHARLES · 2020 to 2021
$253k
CIHRDepartment of HealthMedical Research Council MR/S03546X/1Medical Research Council MR/T027800/1NIA NIH HHS K99 AG065501NIA NIH HHS P01 AG019724NIA NIH HHS P50 AG023501NIA NIH HHS R01 AG045611NIA NIH HHS U01 AG024904NIMH NIH HHS T32 MH019112
6 · The paper itself

Abstract

Alzheimer's disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These 'subtypes' were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of 'typical AD' and a revisiting of tau pathological staging.

Indexed as

AgedAlzheimer DiseaseCarbolinesCerebral CortexCognitive DysfunctionFemaleHumansMaleNeuroimagingPhenotypePositron-Emission TomographyRadiopharmaceuticalsSpatio-Temporal Analysistau Proteins7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indoleCarbolinesRadiopharmaceuticalstau Proteins

Identifiers

PMID33927414
PMCPMC8686688

What OpenQuestion holds

Textmetadata
LicenceTDM
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.