Evidence map›Paper›PMID 41616780›Full record

ArticleCell2026

Molecular features of human pathological tau distinguish tauopathy-associated dementias.

Mukesh Kumar, Christoph N Schlaffner, Shaojun Tang, Maaike A Beuvink, Arthur Viode, Waltraud Mair, Meenakshi Jha, Ceren Uncu, Hendrik Wesseling, Tian Wang and 21 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–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

10 citing papers in PubMed.

  1. From aggregate structure to disease trajectory: the role of the proteostasis network.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026
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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

31 authors.

Mukesh KumarF.M. Kirby Neurobiology Center, Department of Neurobiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Christoph N SchlaffnerF.M. Kirby Neurobiology Center, Department of Neurobiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Data Analytics and Computational Statistics, Hasso Plattner Institute, Digital Engineering Faculty, University of Potsdam, Potsdam, Germany.
Shaojun TangF.M. Kirby Neurobiology Center, Department of Neurobiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Department of Biostatistics, Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Maaike A BeuvinkF.M. Kirby Neurobiology Center, Department of Neurobiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Arthur ViodeDepartments of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Waltraud MairF.M. Kirby Neurobiology Center, Department of Neurobiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Meenakshi JhaDepartments of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Ceren UncuF.M. Kirby Neurobiology Center, Department of Neurobiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Hendrik WesselingF.M. Kirby Neurobiology Center, Department of Neurobiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Tian WangF.M. Kirby Neurobiology Center, Department of Neurobiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Derek H OakleyMassachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Pieter BeerepootF.M. Kirby Neurobiology Center, Department of Neurobiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Jie XueF.M. Kirby Neurobiology Center, Department of Neurobiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Theresa R ConnorsMassachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
David A DavisUMMG Department of Neurology, Miller School of Medicine, Medical Campus, University of Miami, Miami, FL, USA.
Matthew P FroschMassachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Melissa E MurrayDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Salvatore E SpinaMemory and Aging Center, Department of Neurology and Pathology, University of California, San Francisco, San Francisco, CA, USA.
Lea T GrinbergDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
William W SeeleyMemory and Aging Center, Department of Neurology and Pathology, University of California, San Francisco, San Francisco, CA, USA.
Bruce L MillerMemory and Aging Center, Department of Neurology and Pathology, University of California, San Francisco, San Francisco, CA, USA.
Adam L BoxerMemory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Daniel H GeschwindDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Kenneth S KosikNeuroscience Research Institute and Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Bernhard Y RenardData Analytics and Computational Statistics, Hasso Plattner Institute, Digital Engineering Faculty, University of Potsdam, Potsdam, Germany.
Michael DeTureDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Ann C McKeeBoston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA.
Bradley T HymanMassachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Hanno SteenF.M. Kirby Neurobiology Center, Department of Neurobiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Departments of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Judith A SteenF.M. Kirby Neurobiology Center, Department of Neurobiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: judith.steen@childrens.harvard.edu.

Funding

Technology and Remote Assessment CoreU19AG063911 · NIA · MAYO CLINIC ROCHESTER · PI Bradley F Boeve · 2019 to 2026
$120.9M
Early Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3M
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Katherine P Rankin · 2019 to 2026
$36.9M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5M
RL5: Research Education CoreP30AG072978 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Ann C. McKee · 2021 to 2026
$25.6M
Traumatic Brain Injury and Repetitive Head Impacts: Contributions to AD/ADRD and CTE Neuropathology and Resulting Clinical SyndromesU54NS115266 · NINDS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI STEIN, THOR · 2019 to 2023
$10.3M
Early Onset Alzheimer's Disease ConsortiumR56AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2017 to 2017
$7.7M
Molecular Basis of the Tau Aggregation PathwayR01AG056058 · NIA · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI Songi Han, KENNETH Stephen KOSIK · 2017 to 2026
$6.4M
Integrated Platform to study Neurodegeneration in Alzheimer’s DiseaseR01AG071858 · NIA · BOSTON CHILDREN'S HOSPITAL · PI STEEN, JUDITH A · 2021 to 2025
$3.9M
Quantifying post-translational modifications and protein expression by HTP-MSRC4GM096319 · NIGMS · HARVARD MEDICAL SCHOOL · PI KIRSCHNER, MARC WALLACE · 2010 to 2010
$3.8M
Impact of coding and non-coding variation in progressive supranuclear palsyUG3NS104095 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DICKSON, DENNIS WILLIAM, GESCHWIND, DANIEL H · 2017 to 2019
$3.6M
NIA NIH HHS P01 AG019724NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG072978NIA NIH HHS R01 AG056058NIA NIH HHS R01 AG071858NIA NIH HHS R56 AG057195NIA NIH HHS R56 AG061196NIA NIH HHS RF1 AG059789NIA NIH HHS U01 AG057195NIA NIH HHS U19 AG063911NIGMS NIH HHS R01 GM112007NIGMS NIH HHS RC4 GM096319NINDS NIH HHS R01 NS066973NINDS NIH HHS U54 NS115266NINDS NIH HHS UG3 NS104095
6 · The paper itself

Abstract

In Alzheimer's disease (AD), pathological tau protein shows a progressive accumulation of post-translational modifications (PTMs), reflecting disease severity, progression, and prion-like activity. Although many neurodegenerative diseases with dementia display tau aggregates, the pathological proteoforms of tau protein from each disease type remain unknown. Here, using a quantitative mass spectrometry-based proteomics platform, FLEXITau, deep characterization of pathological tau protein isolated from the brains of 203 human subjects with AD, familial AD (fAD), chronic traumatic encephalopathy (CTE), corticobasal degeneration (CBD), Pick's disease (PiD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB)-a non-tauopathy symptomatic control-and healthy controls (CTR) is performed. Unsupervised data analyses and supervised machine learning identify distinct molecular features of pathological tau for each disease, enabling molecular disease stratification. This study identifies potential disease-specific biomarkers and therapeutic targets for tauopathies and provides critical quantitative information for pharmacokinetic modeling required for therapeutic and disease mechanism studies.

Indexed as

DementiaTauopathiestau ProteinsAgedAged, 80 and overAlzheimer DiseaseBiomarkersBrainChronic Traumatic EncephalopathyCorticobasal DegenerationFemaleHumansLewy Body DiseaseMachine LearningMaleMass SpectrometryBiomarkerstau Proteinsbiomarkerscleavagemachine learningmass spectrometryMRMneurodegenerative diseasesproteomicsPTMstau proteintherapeutics

Identifiers

PMID41616780
PMCPMC13075643

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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.