Evidence map›Paper›PMID 42720122›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

TMEM106B is a selective modulator of TDP-43 pathology in Alzheimer's disease.

Madison M Reeves, Anna Calliari, Tiffany W Todd, Candela Maroto Cidfuentes, Karen Jansen-West, Mei Yue, Yuping Song, Judith Dunmore, Bailey Rawlinson, Erica Engelberg-Cook and 12 more

Abstract read
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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

22 authors.

Madison M ReevesDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Anna CalliariDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Tiffany W ToddDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Candela Maroto CidfuentesDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Karen Jansen-WestDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Mei YueDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Yuping SongDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Judith DunmoreDepartment of Neurology, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Bailey RawlinsonDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Erica Engelberg-CookDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Michael DeTureDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Gregory S DayDepartment of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
Neill R Graff-RadfordDepartment of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
Bradley F BoeveDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
David S KnopmanDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Casey N CookDepartment of Molecular Medicine, University of South Florida, Tampa, Florida, USA.
Melissa E MurrayDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Keith A JosephsDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Leonard PetrucelliDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.ORCID https://orcid.org/0000-0003-2959-129X
Mercedes PrudencioDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.ORCID https://orcid.org/0000-0002-4894-4858

Funding

SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
Research Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI KEJAL KANTARCI · 2019 to 2026
$33.5M
Human Biomarkers CoreU54NS123743 · NINDS · STANFORD UNIVERSITY · PI FRATTA, PIETRO, GITLER, AARON D. · 2021 to 2025
$8.2M
Understanding the role of TDP-43 in Alzheimers disease and FTLDR01AG037491 · NIA · MAYO CLINIC ROCHESTER · PI JOSEPHS, KEITH A · 2010 to 2024
$6.5M
Investigating the role of TMEM106b genetics and pathology in Alzheimer’s disease, LATE and FTLDR01NS132330 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Keith A Josephs, LEONARD PETRUCELLI · 2023 to 2026
$4.3M
Expanding insights into FTD disease mechanismsR35NS137447 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI LEONARD PETRUCELLI · 2025 to 2026
$2.3M
Stathmin-2 and TDP-43 neurodegeneration in Alzheimer’s and multi-etiology dementiasR01NS120992 · NINDS · MAYO CLINIC ROCHESTER · PI JOSEPHS, KEITH A, PRUDENCIO, MERCEDES · 2024 to 2025
$1.6M
Alzheimer's Disease Strategic Fund ADSF-24-1284327-CBrightFocus Foundation A2024017SCure Alzheimer's FundNIA NIH HHS P30 AG062677NIA NIH HHS R01 AG037491NIA NIH HHS U01 AG006786NIH HHS P30AG062677NIH HHS R01AG037491NIH HHS R01NS120992NIH HHS R01NS132330NIH HHS R35NS137447NIH HHS U01AG006786NIH HHS U54NS123743NINDS NIH HHS R01 NS120992NINDS NIH HHS R01 NS132330NINDS NIH HHS R35 NS137447NINDS NIH HHS U54 NS123743Target ALS FoundationThe Kissick Family Foundation
6 · The paper itself

Abstract

introductionCo-pathologies - including Lewy body, vascular, and TDP-43 lesions - are common in Alzheimer's disease (AD), contributing to its clinical and pathological heterogeneity. Genetic risk factors may drive mixed pathology presentation, but their influence on the development of specific co-pathologies remains unclear.

methodsWe evaluated the TMEM106B coding variant rs3173615 and apolipoprotein E (APOE) diplotype (rs429358, rs7412) in post mortem brains from 2604 individuals with a primary neuropathologic diagnosis of AD. Binary logistic regression models linked each genetic modifier with co-pathology risk.

resultsThe TMEM106B risk variant was significantly enriched in AD cases with transactive response DNA-binding protein 43 kDa (TDP-43) pathology - associating with increased odds of developing AD TDP-43 subtype α - but failed to associate with Lewy body or vascular pathology. In contrast, APOE ε4 associated with increased risk for multiple co-pathologies in AD. DISCUSSION: We find that genetic factors individually influence AD pathological heterogeneity: TMEM106B selectively modulates TDP-43 co-pathology, while APOE ε4 appears broadly permissive to co-pathology development.

Indexed as

Alzheimer DiseaseBrainDNA-Binding ProteinsMembrane ProteinsNerve Tissue ProteinsAgedAged, 80 and overFemaleGenetic Predisposition to DiseaseHumansMalePolymorphism, Single NucleotideDNA-Binding ProteinsMembrane ProteinsNerve Tissue ProteinsTARDBP protein, humanTMEM106B protein, humanAluYb8Alzheimer's diseaseAPOEapolipoprotein Eco‐pathologiesgeneticslimbic‐predominant age‐related TDP‐43 encephalopathy (LATE)neurodegenerative diseaseTMEM106Btransactive response DNA‐binding protein 43 (TDP‐43)

Identifiers

PMID42720122
PMCPMC13559991

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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.