Evidence map›Paper›PMID 40667715›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Genome-wide association of tau neuroimaging and plasma biomarkers in adults with Down syndrome.

Kang-Hsien Fan, Ruyu Shi, Asma Naseer Cheema, Lam-Ha T Dang, Laura Xicota, Sharon Krinsky-McHale, M Muaaz Aslam, Narges Zafari, Vibha Acharya, Eleanor Feingold and 10 more

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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Genome-wide association of tau neuroimaging and plasma biomarkers in adults with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
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

20 authors.

Kang-Hsien FanDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Ruyu ShiDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.ORCID 0009-0004-3230-2625
Asma Naseer CheemaDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Lam-Ha T DangSergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Laura XicotaSergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Sharon Krinsky-McHaleDepartment of Psychology, New York Institute for Basic Research, Staten Island, New York, USA.
M Muaaz AslamDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Narges ZafariDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Vibha AcharyaDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Eleanor FeingoldDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Charles M LaymonDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Ann CohenDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Benjamin L HandenDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Bradley T ChristianWaisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Elizabeth HeadDepartment of Pathology and Laboratory Medicine, School of Medicine, University of California, Irvine, Irvine, California, USA.
Mark E MapstoneDepartment of Neurology, School of Medicine, University of California, Irvine, Irvine, California, USA.
Alzheimer's Biomarker Consortium – Down Syndrome (ABC‐DS)
Carlos CruchagaDepartment of Psychiatry, School of Medicine, Washington University, St. Louis, Missouri, USA.
Joseph H LeeSergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
M Ilyas KambohDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Funding

University of Pittsburgh Clinical and Translational Science InstituteUL1TR001857 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2016 to 2025
$129.3M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
Project 3: Biomarkers for DS Clinical TrialsU19AG068054 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TUDORASCU, DANA L · 2020 to 2025
$103.7M
Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
University of Wisconsin Institute for Clinical and Translational ResearchUL1TR002373 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI ELIZABETH S BURNSIDE, Allan R. Brasier · 2017 to 2026
$75.9M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1M
Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
TREATMENT OF DEPRESSION IN ALZHEIMER'S DISEASEP50AG005133 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SWEET, ROBERT A · 1985 to 2019
$43.0M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5M
University of California Health Participation in the National COVID Cohort Collaborative (N3C)UL1TR001414 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M, VILAIN, ERIC J. · 2015 to 2023
$35.1M
Wisconsin Alzheimer's Disease Research CenterP30AG062715 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Sanjay Asthana · 2019 to 2026
$34.5M
Alzheimer's Disease Research Centers Program P30AG062421Alzheimer's Disease Research Centers Program P30AG062715Alzheimer's Disease Research Centers Program P30AG066519Alzheimer's Disease Research Centers Program P50AG005133Alzheimer's Disease Research Centers Program P50AG005681Alzheimer's Disease Research Centers Program P50AG008702Alzheimer's Disease Research Centers Program P50AG16537Eunice Kennedy Shriver Intellectual and Developmental Disability Research Centers Program U54HD087011Eunice Kennedy Shriver Intellectual and Developmental Disability Research Centers Program U54HD090256NCATS NIH HHS UL1 TR001414NCATS NIH HHS UL1TR001414NCATS NIH HHS UL1 TR001857NCATS NIH HHS UL1TR001857NCATS NIH HHS UL1 TR001873NCATS NIH HHS UL1TR001873NCATS NIH HHS UL1 TR002345NCATS NIH HHS UL1 TR002373NCATS NIH HHS UL1TR002373NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066519NIA NIH HHS P50 AG005133NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008702NIA NIH HHS R01 AG064877NIA NIH HHS R01AG064877NIA NIH HHS R56 AG064877NIA NIH HHS U01 AG051406NIA NIH HHS U01AG051406NIA NIH HHS U01 AG051412NIA NIH HHS U01AG051412NIA NIH HHS U19 AG068054NIA NIH HHS U19AG068054NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG21886NICHD NIH HHS P50 HD105353NICHD NIH HHS U54 HD087011NICHD NIH HHS U54 HD090256
6 · The paper itself

Abstract

introductionPlasma biomarkers in Down syndrome (DS) accurately detect Alzheimer's disease (AD) pathology. This study aimed to identify genetic loci associated with plasma tau biomarkers (phosphorylated tau [p-tau]181, p-tau217, total tau [t-tau]) and tau positron emission tomography (PET) in DS.

methodsWe examined 375 people with DS from the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) with data on all four tau biomarkers, and 133 subjects from another study of DS with plasma t-tau. Single-trait and multi-trait genetic association analyses were conducted. AD polygenic risk scores (PRSs) were tested with tau biomarkers.

resultsThree genome-wide significant associations were identified for p-tau181: TUBAP/rs76523946, P = 2.21E-08; CTNND2/rs142510573, P = 3.04E-08; CLSTN2/rs112448655, P = 3.04E-08, and one for t-tau (JHY/rs77264104, P = 2.84E-08). AD PRS was associated with higher concentrations of tau PET (β = 0.30, P = 6.57E-04), p-tau217 (β = 0.11, P = 4.10E-02), and t-tau (β = 0.12, P = 3.60E-02). DISCUSSION: These data indicate the presence of novel genetic loci in DS affecting plasma tau biomarkers and that AD risk PRS may modify tau neuroimaging and plasma biomarkers in DS. HIGHLIGHTS: Four loci were linked to plasma total tau (t-tau) or phosphorylated tau (p-tau)181 with genome-wide significance. JHY/rs77264104 stays genome-wide significant for plasma t-tau in a meta genome-wide association study (GWAS). Alzheimer's disease (AD) polygenic risk score is associated with tau positron emission tomography (PET), regardless of apolipoprotein E genotype and region. Tau-PET genes in Down syndrome (DS) are enriched in the cerebrospinal fluid phosphorylated tau Alzheimer's disease dementia GWAS catalog. T-tau genes in DS are enriched in a verbal memory GWAS catalog within a mild cognitive impairment cohort.

Indexed as

Down SyndromeGenome-Wide Association Studytau ProteinsAdultAlzheimer DiseaseBiomarkersFemaleHumansMaleMiddle AgedNeuroimagingPositron-Emission TomographyBiomarkersMAPT protein, humantau ProteinsAlzheimer's diseaseDown syndromegenome‐wide association studynovel genetic locitau biomarkerstrisomy 21

Identifiers

PMID40667715
PMCPMC12264832

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