ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2018
Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms.
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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 6 of them syntheses that pooled it.
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91 citing papers in PubMed, 6 syntheses or guidelines pooled it.
- A bibliometric and visual analysis of the impact of senescence on tumor immunotherapy.Frontiers in immunology · 2025Pooled it
- Prediction of clinical diagnosis of Alzheimer's disease, vascular, mixed, and all-cause dementia by a polygenic risk score and APOE status in a community-based cohort prospectively followed over 17 years.Molecular psychiatry · 2021Pooled it
- Microglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer's Disease Genetics.Trends in neurosciences · 2020Pooled it
- Interpretation of risk loci from genome-wide association studies of Alzheimer's disease.The Lancet. Neurology · 2020Pooled it
- From Polygenic Scores to Precision Medicine in Alzheimer's Disease: A Systematic Review.Journal of Alzheimer's disease : JAD · 2020Pooled it
- The genetic risk of Alzheimer's disease beyond APOE ε4: systematic review of Alzheimer's genetic risk scores.Translational psychiatry · 2018Pooled it
- Guilingji capsule for Alzheimer's disease: secondary analysis of a randomized non-inferiority controlled trial.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2023Trial
- Atypical Alzheimer disease: a multi-axis framework toward defining heterogeneity.Nature reviews. Neurology · 2026Review
- Machine learning-derived Alzheimer's disease dimensions: neuroanatomical, cognitive, clinical, functional, and genetic risk heterogeneity signatures.medRxiv : the preprint server for health sciences · 2026Article
- APOE and genetic risk variants influence Alzheimer's disease onset in carriers of an extra copy of APP, with and without Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Toward personalized medicine in AD/ADRD through genetic-exposome dementia risk assessments.NPJ dementia · 2026Review
- Alzheimer's disease polygenic risk in early- and late-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- 15 years of longitudinal genetic, clinical, cognitive, imaging, and biochemical measures in DIAN.NPJ dementia · 2026Article
- Advances in Genetic Risk Scores for Alzheimer's Disease and Dementia: A Systematic Review.Neurology international · 2025Review
- Novel early-onset Alzheimer-associated genes influence risk through dysregulation of glutamate, immune activation, and intracellular signaling pathways.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The neurobiological foundation of effective repetitive transcranial magnetic brain stimulation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Research models to study lewy body dementia.Molecular neurodegeneration · 2025Review
- Blood biomarker profiles in young-onset neurocognitive disorders: A cohort study.The Australian and New Zealand journal of psychiatry · 2025Article
- Addressing overfitting bias due to sample overlap in polygenic risk scoring.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Somatic and Stem Cell Bank to study the contribution of African ancestry to dementia: African iPSC Initiative.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors.
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA.
Jorge L Del-AguilaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Benjamin SaefDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Kathleen BlackDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Maria Victoria FernandezDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
John BuddeDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Laura IbanezDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Yuetiva DemingDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Manav KapoorRonald M. Loeb Center for Alzheimer's Disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Giuseppe TostoTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, NY, USA; Gertrude H. Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, NY, USA; Department of Neurology, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, NY, USA.
Richard P MayeuxTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, NY, USA; Gertrude H. Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, NY, USA; School of Medicine, Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic.
David M HoltzmanDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Anne M FaganDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
John C MorrisDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Randall J BatemanDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Alison M GoateRonald M. Loeb Center for Alzheimer's Disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Dominantly Inherited Alzheimer Network (DIAN)
Disease Neuroimaging Initiative (ADNI)
NIA-LOAD family study
Oscar HarariDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: harario@wustl.edu.
Funding
Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI ARTHUR W TOGA · 2016 to 2026
$226.7MWashington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0MAlzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0MNational 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
$119.8MWU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI Tammie Lee Smith Benzinger · 1985 to 2026
$69.5MImaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9MWASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1MThe natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI SCHINDLER, SUZANNE ELIZABETH · 2005 to 2025
$49.5MWashington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4MVASCULAR RISK AND COGNITIVE STATUS IN A LATINO POPULATIONP50AG005142 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ARANDA, MARIA P. · 1985 to 2019
$41.0MVESICULAR LOCALIZATION AND FUNCTION OF PRESENILIN 1 FRAGMENTP50AG005138 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI SCHIMMING, CORBETT · 1985 to 2019
$37.9MMedical Research Council MR/L023784/1NCATS NIH HHS UL1 TR000448NCATS NIH HHS UL1 TR002345NCI NIH HHS P30 CA091842NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG066514NIA NIH HHS P50 AG005138NIA NIH HHS P50 AG005142NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG016570NIA NIH HHS R01 AG035083NIA NIH HHS R01 AG041797NIA NIH HHS R01 AG044546NIA NIH HHS RF1 AG015473NIA NIH HHS RF1 AG044546NIA NIH HHS RF1 AG053303NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG058922NIA NIH HHS U19 AG024904NIA NIH HHS U19 AG032438NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG056270NIDA NIH HHS R25 DA027995NIH HHS S10 OD018522NINDS NIH HHS R01 NS085419
Abstract
objectiveTo determine whether the extent of overlap of the genetic architecture among the sporadic late-onset Alzheimer's Disease (sLOAD), familial late-onset AD (fLOAD), sporadic early-onset AD (sEOAD), and autosomal dominant early-onset AD (eADAD).
methodsPolygenic risk scores (PRSs) were constructed using previously identified 21 genome-wide significant loci for LOAD risk.
resultsWe found that there is an overlap in the genetic architecture among sEOAD, fLOAD, and sLOAD. The highest association of the PRS and risk (odds ratio [OR] = 2.27; P = 1.29 × 10
conclusionOur analysis confirms that the genetic factors identified for LOAD modulate risk in sLOAD and fLOAD and also sEOAD cohorts. Specifically, our results suggest that the burden of these risk variants is associated with familial clustering and earlier onset of AD. Although these variants are not associated with risk in the eADAD, they may be modulating age at onset.
Indexed as
Family HealthAdultAgedAged, 80 and overAge of OnsetAlzheimer DiseaseAmyloid beta-PeptidesApolipoproteins ECohort StudiesDatabases, BibliographicFemaleGenetic Predisposition to DiseaseGenotypeHumansLogistic ModelsMaleAmyloid beta-Peptidesamyloid beta-protein (1-42)Apolipoproteins EPeptide Fragmentstau ProteinsAge at onsetAPOEAPPArea under the curveAβCerebrospinal fluidDisease modifierDominantly inherited Alzheimer networkEarly-onset Alzheimer's diseaseEarly-onset autosomal dominantGenetic architectureGenetic risk factorLate-onset Alzheimer's diseasePolygenic risk scorePSEN1PSEN2Sporadic late-onset Alzheimer's diseaseTau
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