Evidence map›Paper›PMID 41532810›Full record

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

Alzheimer's disease polygenic risk in early- and late-onset Alzheimer's disease.

Julian V Pentchev, Trever Jackson, Naazneen Khan, Thea J Rosewood, Yen-Ning Huang, Kwangsik Nho, Andrew J Saykin, Ani Eloyan, Alexander Taurone, Maryanne Thangarajah and 47 more

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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. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Alzheimer's disease polygenic risk in early- and late-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
4 · The record

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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

57 authors.

Julian V PentchevDepartment of Neurology, Indiana University School of Medicine, Indianapolis, USA.
Trever JacksonDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, USA.
Naazneen KhanDepartment of Neurology, Indiana University School of Medicine, Indianapolis, USA.
Thea J RosewoodIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, USA.
Yen-Ning HuangIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, USA.
Kwangsik NhoIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, USA.
Andrew J SaykinDepartment of Neurology, Indiana University School of Medicine, Indianapolis, USA.
Ani EloyanCenter for Statistical Sciences, Brown University, Providence, USA.
Alexander TauroneCenter for Statistical Sciences, Brown University, Providence, USA.
Maryanne ThangarajahCenter for Statistical Sciences, Brown University, Providence, USA.
Meghan RiddleDepartment of Neurology, Alpert Medical School, Brown University, Providence, USA.
Steven SallowayDepartment of Neurology, Alpert Medical School, Brown University, Providence, USA.
Alireza AtriBanner Sun Health Research Institute, Sun City, USA.
Lawrence S HonigDepartment of Neurology, Columbia University Irving Medical Center, New York, USA.
Erik C B JohnsonDepartment of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, USA.
Raymond Scott TurnerDepartment of Neurology, Georgetown University, Washington D.C., USA.
Joseph C MasdeuNantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, USA.
Tatiana M ForoudDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, USA.
David ClarkDepartment of Neurology, Indiana University School of Medicine, Indianapolis, USA.
Dustin B HammersDepartment of Neurology, Indiana University School of Medicine, Indianapolis, USA.
Jeffrey L DageDepartment of Neurology, Indiana University School of Medicine, Indianapolis, USA.
Kala KirbyDepartment of Neurology, Indiana University School of Medicine, Indianapolis, USA.
Bernardino GhettiIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, USA.
Kathy NewellIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, USA.
Chiadi U OnyikeDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, USA.
Gregory S DayDepartment of Neurology, Mayo Clinic, Jacksonville, USA.
Neill R Graff-RadfordDepartment of Neurology, Mayo Clinic, Jacksonville, USA.
Melissa E MurrayDepartment of Neuroscience, Mayo Clinic, Jacksonville, USA.
David T JonesDepartment of Neurology, Mayo Clinic, Rochester, USA.
Clifford R JackDepartment of Radiology, Mayo Clinic, Rochester, USA.
Prashanthi VemuriDepartment of Radiology, Mayo Clinic, Rochester, USA.
Alexandra TouroutoglouDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
Ranjan DuaraWien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami, USA.
Ian GrantDepartment of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, USA.
Sharon ShaDepartment of Neurology & Neurological Sciences, Stanford University, Palo Alto, USA.
Thomas S WingoDepartment of Neurology, University of California, Davis, USA.
Laurel A BeckettDepartment of Public Health Sciences, University of California, Davis, USA.
Emily RogalskiDepartment of Neurology, Healthy Aging & Alzheimer's Research Care Center, University of Chicago, Chicago, USA.
Mario F MendezDepartment of Neurology, University of California, Los Angeles, USA.
Joel KramerDepartment of Neurology, University of California, San Francisco, USA.
Renaud La JoieDepartment of Neurology, University of California, San Francisco, USA.
Ganna BlazhenetsDepartment of Neurology, University of California, San Francisco, USA.
Lea T GrinbergDepartment of Neurology, University of California, San Francisco, USA.
Robert KoeppeDepartment of Radiology, University of Michigan, Ann Arbor, USA.
David A WolkDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Paul AisenAlzheimer's Therapeutic Research Institute, University of Southern California, San Diego, USA.
Rema RamanAlzheimer's Therapeutic Research Institute, University of Southern California, San Diego, USA.
Arthur TogaLaboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Los Angeles, USA.
Walter A KukullDepartment of Epidemiology, University of Washington, Seattle, USA.
Erik MusiekDepartment of Neurology, Washington University in St. Louis, St. Louis, USA.
Kyle B WomackDepartment of Neurology, Washington University in St. Louis, St. Louis, USA.
Maria C CarrilloMedical & Scientific Relations Division, Alzheimer's Association, Chicago, USA.
Gil D RabinoviciDepartment of Neurology, University of California, San Francisco, USA.
Bradford C DickersonDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
Liana G ApostolovaDepartment of Neurology, Indiana University School of Medicine, Indianapolis, USA.
Kelly N H NudelmanDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, USA.
Longitudinal Early‐Onset Alzheimer's Disease Study Consortium and the Alzheimer's Disease Neuroimaging Initiative

Funding

Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI MICHAEL W WEINER · 2016 to 2026
$226.7M
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
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
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
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
'T V ASSESSMENT - MEMORY DISORDERED PATIENTS'P50AG005146 · NIA · JOHNS HOPKINS UNIVERSITY · PI BANDEEN-ROCHE, KAREN J. · 1985 to 2019
$37.6M
Research Education ComponentP30AG010133 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 1991 to 2020
$37.3M
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
UPenn ADCC Biomarker CoreP30AG010124 · NIA · UNIVERSITY OF PENNSYLVANIA · PI VAN DEERLIN, VIVIANNA M · 1991 to 2020
$35.1M
Neuropathology CoreP30AG013854 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI VASSAR, ROBERT J · 1996 to 2020
$28.9M
Alzheimer's Association research (AARG)-22-926940Alzheimer's Association research GENETICS-19-639372Alzheimer's Association research LDRFP-21-818464NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG072976NIA NIH HHS P50 AG005146NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG023501NIA NIH HHS P50 AG025688NIA NIH HHS P50 AG047366NIA NIH HHS R56 AG057195NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG057195NIA NIH HHS U19 AG024904NIA NIH HHS U24 AG021886NIH HHS P30AG010124NIH HHS P30AG010133NIH HHS P30AG013854NIH HHS P30AG062421NIH HHS P30AG062422NIH HHS P30AG066506NIH HHS P30AG072976NIH HHS P50AG005146NIH HHS P50AG005681NIH HHS P50AG008702NIH HHS P50AG023501NIH HHS P50AG025688NIH HHS P50AG047366NIH HHS R56AG057195NIH HHS U01AG016976NIH HHS U01AG6057195NIH HHS U19AG024904NIH HHS U24AG021886U.S. Department of Defense W81XWH-12-2-0012
6 · The paper itself

Abstract

introductionThe genetic basis of sporadic early-onset Alzheimer's disease (EOAD) remains largely unknown, prompting evaluation of late-onset Alzheimer's disease (LOAD) polygenic risk in EOAD.

methodsA LOAD polygenic score (PGS) was calculated in the Longitudinal Early-onset Alzheimer's Disease Study (LEADS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) study and tested for associations with AD risk, cognitive performance, and imaging and fluid biomarkers.

resultsThough PGS was elevated in LOAD and EOAD, it was not a significant predictor of EOAD adjusting for APOE ε4 carrier status and was not associated with age of EOAD onset (p = 0.106) or with cognitive performance (p = 0.417). In LEADS, greater LOAD PGS was associated with differences in neuroimaging and fluid biomarkers, including elevated synaptosomal-associated protein 25 (SNAP-25) (p = 2.3 × 10 DISCUSSION: While LOAD polygenic risk contributed minimally to EOAD onset and cognitive dysfunction, PGS association with fluid biomarkers in LEADS suggests a role for LOAD polygenic risk in EOAD pathophysiology. HIGHLIGHTS: LOAD PGSs were elevated in both LOAD and EOAD compared to controls; however, LOAD PGS did not significantly predict EOAD risk, age at onset, or cognitive performance independent of APOE ε4 in the LEADS. Higher LOAD PGS was associated with lower amyloid PET Centiloids (less brain amyloid deposition) as well as lower CSF biomarker Aβ42 in LEADS (proxy marker suggesting higher brain amyloid deposition) in LEADS; these contradictory findings support the need for larger studies to further investigate whether LOAD PGS is associated with increased amyloid deposition in EOAD. Higher LOAD PGS was also associated with higher levels of CSF synaptosomal-associated protein 25 (SNAP-25), a key component of the SNARE complex, suggesting that LOAD genetic factors may contribute to dysregulation of synaptic transmission and/or pathological protein aggregation in EOAD.

Indexed as

Alzheimer DiseaseMultifactorial InheritanceAgedAge of OnsetAmyloid beta-PeptidesApolipoprotein E4BiomarkersBrainFemaleGenetic Predisposition to DiseaseGenetic Risk ScoreHumansLongitudinal StudiesMaleSynaptosomal-Associated Protein 25Amyloid beta-PeptidesApolipoprotein E4BiomarkersSynaptosomal-Associated Protein 25Alzheimer's diseaseearly onsetgeneticspolygenic

Identifiers

PMID41532810
PMCPMC12802089

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