Evidence map›Paper›PMID 40667702›Full record

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

Genome-wide association analyses identify candidate loci for amyloid imaging and plasma biomarkers in adults with Down syndrome.

M Muaaz Aslam, Lam-Ha T Dang, Ruyu Shi, Kang-Hsien Fan, Asma Naseer Cheema, Laura Xicota, Danveet Minhas, Weiquan Luo, Narges Zafari, Vibha Acharya and 12 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis 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, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 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

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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.

M Muaaz AslamDepartment of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, USA.ORCID 0000-0003-1817-7894
Lam-Ha T DangSergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Ruyu ShiDepartment of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, USA.ORCID 0009-0004-3230-2625
Kang-Hsien FanDepartment of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, USA.
Asma Naseer CheemaDepartment of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, USA.
Laura XicotaSergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Danveet MinhasDepartment of Radiology and Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Weiquan LuoDepartment of Radiology and Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Narges ZafariDepartment of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, USA.
Vibha AcharyaDepartment of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, USA.
Eleanor FeingoldDepartment of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, USA.
Sharon Krinsky-McHaleDepartment of Psychology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA.
Charles M LaymonDepartment of Radiology and Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Ann CohenDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Benjamin L HandenDepartment of Psychiatry, University of Pittsburgh School of Medicine, 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, California, USA.
Mark E MapstoneDepartment of Neurology, School of Medicine, University of California, Irvine, California, USA.
Alzheimer's Biomarker Consortium – Down Syndrome (ABC‐DS)Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Joseph H LeeSergievsky Center, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
M Ilyas KambohDepartment of Human Genetics, University of Pittsburgh School of Public Health, 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 LEE, JOSEPH HYUNGWOO · 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 P50 AG16537NCATS NIH HHS UL1 TR001414NCATS NIH HHS UL1 TR001857NCATS NIH HHS UL1 TR001873NCATS NIH HHS UL1 TR002345NCATS NIH HHS UL1 TR002373NIA 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 AG014673NIA NIH HHS R01 AG064877NIA NIH HHS R01AG064877NIA NIH HHS R56 AG061837NIA 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 U24AG21886NICHD NIH HHS P01 HD035897NICHD NIH HHS P50 HD105353NICHD NIH HHS U54 HD087011NICHD NIH HHS U54 HD090256
6 · The paper itself

Abstract

backgroundPeople with Down syndrome (DS) overproduce amyloid-beta (Aβ) due to triplication of the amyloid precursor protein (APP) gene on chromosome 21, and consequently accumulate brain amyloid load at younger ages. We conducted genome-wide association (GWA) analyses on amyloid imaging and plasma biomarkers to discern the genetic architecture of amyloid burden in DS.

methodsGWA analyses were performed on amyloid positron emission tomography (PET) and plasma biomarkers (Aβ40, Aβ42, Aβ42/40 ratio) in participants from the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) and on plasma Aβ biomarkers available in an independent DS cohort, followed by meta-analysis of plasma Aβ biomarker data.

resultsMeta-analysis on plasma biomarkers identified four novel loci: two for Aβ42 (PFKFB3/rs147647642, p = 2.83E-08; DLX3-PICART1/rs12952028, p = 9.31E-09) and two for Aβ40 (LINC01941-GYPC/rs78338676, p = 9.33E-09; PDE4D/rs146261781, p = 9.97E-08). Five genome-wide signals were observed for amyloid-PET in the ABC-DS cohort that need confirmation in an independent DS dataset. DISCUSSION: Despite the small sample, our findings highlight the unique genetic architecture of amyloid burden in DS. HIGHLIGHTS: Genetic markers for amyloid biomarkers in Down syndrome (DS) were identified. Meta-analyses identified four novel loci for plasma amyloid in two DS cohorts. Five loci associated with amyloid positron emission tomography levels were identified in the Alzheimer's Biomarker Consortium-Down Syndrome cohort. Multi-trait analysis revealed loci linking variants to amyloid biomarkers.

Indexed as

Amyloid beta-PeptidesBrainDown SyndromeGenome-Wide Association StudyAdultBiomarkersCohort StudiesFemaleHumansMaleMiddle AgedPeptide FragmentsPolymorphism, Single NucleotidePositron-Emission TomographyAmyloid beta-Peptidesamyloid beta-protein (1-42)BiomarkersPeptide FragmentsAD biomarkeramyloid‐PETCentiloidplasma Aβtrisomy 21

Identifiers

PMID40667702
PMCPMC12265027

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.