ArticleBrain : a journal of neurology2025
The landscape of autosomal-dominant Alzheimer's disease: global distribution and age of onset.
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Article in Brain : a journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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18citing papers in PubMed, 1 pooled it
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Genetic Risk in Multiple Sclerosis: Susceptibility, Modifiers and Unresolved Questions.Neurology and therapy · 2026Review
- Technology-natives and technology-adopters: Age differences in remote cognitive assessment in Alzheimer disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- NovelWorld journal of radiology · 2026Article
- Considerations for the selection and phenotyping of mouse models for the study of Alzheimer's disease.STAR protocols · 2026Review
- The many meanings of Alzheimer's disease and why they matter for policy, research, and care.GeroScience · 2026Article
- Statistical models for Alzheimer's disease clinical trials: Lessons learned from the DIAN-TU Platform Trial.Journal of Alzheimer's disease : JAD · 2026Article
- Recommendations for genetic counseling for individuals at risk of autosomal dominant Alzheimer's disease in Latin America.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Effect of Cognitive Reserve on Age at Symptom Onset and Cognitive Decline in Individuals With Dominantly Inherited Alzheimer Disease.Neurology · 2026Article
- Advances in hiPSC-Derived Brain Organoids as a Model to Study Neuroinflammation in Alzheimer's Disease.Journal of neurochemistry · 2026Review
- Abnormalities in core AD biomarkers precede inflammatory and glial markers in CSF in Autosomal Dominant Alzheimer's Disease.medRxiv : the preprint server for health sciences · 2026Article
- Presymptomatic plasma biomarkers in autosomal dominant Alzheimer's disease: sequence and timing.medRxiv : the preprint server for health sciences · 2026Article
- Cortical asymmetry in autosomal dominant Alzheimer's disease progression.Brain communications · 2026Article
- Toward personalized medicine in AD/ADRD through genetic-exposome dementia risk assessments.NPJ dementia · 2026Review
- The role of genomic-informed risk assessments in predicting dementia outcomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The Bad Medicine of Doctored.JAMA · 2025Article
- "It seems enormously valuable to me." Perspectives of Dutch (potential) carriers of genetic FTD on onset-predictive biomarker testing.Alzheimer's research & therapy · 2025Article
- Lecanemab in symptomatic PSEN1 p.Met233Val early-onset Alzheimer's disease: Neuroimaging safety, regional amyloid-PET dynamics, and longitudinal plasma biomarkers.Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Authors and funding
52 authors.
Haiyan LiuDepartment of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.ORCID 0000-0002-3154-8285
Thomas W MarshDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA.
Xinyu ShiDivision of Biostatistics, Washington University School of Medicine, St Louis, MO 63110, USA.
Alan E RentonRonald M. Loeb Center for Alzheimer's Disease, Department of Genetics and Genomic Sciences, and Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Kevin M BowlingDepartment of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
Ellen ZiegemeierDepartment of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
Guoqiao WangDivision of Biostatistics, Washington University School of Medicine, St Louis, MO 63110, USA.
Yuchen CaoDivision of Biostatistics, Washington University School of Medicine, St Louis, MO 63110, USA.
Alisha AristelRonald M. Loeb Center for Alzheimer's Disease, Department of Genetics and Genomic Sciences, and Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Jessie LiDepartment of Medicine, University of Missouri, Columbia, MO 65212, USA.
Alexa DicksonDepartment of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
Richard J PerrinDepartment of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
Alison M GoateRonald M. Loeb Center for Alzheimer's Disease, Department of Genetics and Genomic Sciences, and Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Victoria FernándezFundacio ACE, Institut Catala de Neurosciencies Aplicades, Barcelona 08028, Spain.
Gregory S DayDepartment of Neurology, Mayo Clinic in Florida, Jacksonville, FL 32224, USA.
Michelle DoeringBernard Becker Medical Library, Washington University School of Medicine, St Louis, MO 63110, USA.
Alisha DanielsDepartment of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
Brian A GordonDepartment of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA.ORCID 0000-0003-2109-2955
Tammie L S BenzingerDepartment of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA.
Jason HassenstabDepartment of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
Laura IbanezDepartments of Psychiatry and Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.ORCID 0000-0003-2381-7059
Charlene Supnet-BellDepartment of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
Chengjie XiongDivision of Biostatistics, Washington University School of Medicine, St Louis, MO 63110, USA.
Ricardo AllegriDepartment of Cognitive Neurology, Instituto Neurológico Fleni, Buenos Aires C1428AQK, Argentina.
Sarah B BermanDepartment of Neurology and Clinical & Translational Science, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Nick C FoxDepartment of Neurodegenerative Disease and UK Dementia Research Institute at Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Natalie S RyanDepartment of Neurodegenerative Disease and UK Dementia Research Institute at Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Edward D HueyDepartment of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI 02903, USA.
Jonathan VögleinDepartment of Neurology, LMU University Hospital, LMU Munich, Munich 81377, Germany.ORCID 0000-0002-5965-838X
James M NobleTaub Institute for Research on Alzheimer's disease and the Aging Brain, GH Sergievsky Center, Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Jee Hoon RohDepartments of Neurology and Physiology, Korea University Anam Hospital, Korea University College of Medicine, Seoul 02841, South Korea.ORCID 0000-0002-3243-0529
Mathias JuckerGerman Center for Neurodegenerative Diseases (DZNE), Tübingen 72076, Germany.
Christoph LaskeGerman Center for Neurodegenerative Diseases (DZNE), Tübingen 72076, Germany.
Takeshi IkeuchiBrain Research Institute, Niigata University, Niigata 951-8585, Japan.ORCID 0000-0001-8828-8085
Raquel Sanchez-ValleRaquel Sánchez-Valle, Alzheimer's and other cognitive disorders unit, Hospital Clínic de Barcelona, FRCB-IDIBAPS, University of Barcelona, Barcelona 08036, Spain.ORCID 0000-0001-7750-896X
Peter R SchofieldNeuroscience Research Australia, Sydney, NSW 2031, Australia.
Patricio Chrem MendezDepartment of Neurology, Institute for Neurological Research Fleni, Buenos Aires C1428AQK, Argentina.
Jasmeer P ChhatwalMassachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0002-7792-1698
Martin FarlowDepartment of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Jae-Hong LeeAsian Medical Center, Seoul 05278, South Korea.
Allan I LeveyGoizueta Alzheimer's Disease Research Center, Emory University, Atlanta, GA 30329, USA.
Johannes LevinDepartment of Neurology, LMU University Hospital, LMU Munich, Munich 81377, Germany.ORCID 0000-0001-5092-4306
Francisco LoperaGroup of Neuroscience of Antioquia, GNA, Medical School, University of Antioquia, Medellin 050010, Colombia.
Ralph MartinsAgeing and Alzheimer's Disease Center, Edith Cowan University, Perth, Western Australia 6027, Australia.
Yoshiki NiimiUnit for Early and Exploratory Clinical Development, University of Tokyo Hospital, Tokyo 113-8655, Japan.
Pedro Rosa-NetoMcGill University Research Centre for Studies in Aging, Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, QC H4H 1R3, Canada.ORCID 0000-0001-9116-1376
John C MorrisDepartment of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.ORCID 0000-0003-2967-9662
Randall J BatemanDepartment of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.ORCID 0000-0002-7729-1702
Celeste M KarchDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA.ORCID 0000-0002-5261-689X
Eric McDadeDepartment of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
Jorge J Llibre-GuerraDepartment of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
Funding
DIAN-TU: Tau Next Generation Prevention Trial - Administrative SupplementR01AG068319 · NIA · WASHINGTON UNIVERSITY · PI RANDALL J BATEMAN · 2020 to 2026
$81.4MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5MImaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9MThe natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5MResearch Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Carolyn Wei Zhu · 2020 to 2026
$31.0MResearch Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Miguel Arce · 2020 to 2026
$30.1MResearch Education ComponentP30AG066444 · NIA · WASHINGTON UNIVERSITY · PI DAVID M. HOLTZMAN · 2020 to 2026
$28.7MPET Imaging of Neuroinflammation in Genetic Alzheimer's DiseaseR01AG052550 · NIA · WASHINGTON UNIVERSITY · PI Beau M Ances, Tammie Lee Smith Benzinger · 2018 to 2026
$4.2MGenetic basis of neuropsychiatric symptoms in Alzheimer's diseaseU01AG079850 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Gary Wayne Beecham, Edward D Huey · 2023 to 2026
$3.0MNeuroanatomical associations with the factor structure underlying neuropsychiatric symptoms in Alzheimer's diseaseR01AG062268 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HUEY, EDWARD D · 2018 to 2022
$2.5MUsing RDoC Negative and Positive Valence Paradigms to Investigate the Mechanisms of Neuropsychiatric Symptoms (NPS) in Alzheimer's Disease and Related DementiasR01MH120794 · NIMH · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HUEY, EDWARD D · 2019 to 2023
$2.1MUnderstanding Alzheimer disease heterogeneity in Hispanic populations.K01AG073526 · NIA · WASHINGTON UNIVERSITY · PI Jorge Jesus Llibre-Guerra · 2022 to 2026
$511kAlzheimer's Association SG-20-690363-DIANGerman Center for Neurodegenerative DiseasesMinistry of Health & Welfare and Ministry of Science and ICT, Republic of Korea RS-2024-00344521Neurological ResearchNIA NIH HHS K01 AG073526NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066514NIA NIH HHS R01 AG052550NIA NIH HHS R01 AG062268NIA NIH HHS R01 AG068319NIA NIH HHS U01 AG079850NIA NIH HHS U19 AG032438NIMH NIH HHS R01 MH120794The Dominantly Inherited Alzheimer Network U19AG032438
Abstract
We present a comprehensive global analysis of genetic variants associated with autosomal-dominant Alzheimer's disease (ADAD). A total of 550 variants in the APP, PSEN1 and PSEN2 genes were identified, of which 279 were classified as pathogenic or likely pathogenic based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria, utilizing data from the Dominantly Inherited Alzheimer Network (DIAN), literature and public databases. Symptomatic age at onset (AAO) data were estimated for 227 of these variants, allowing detailed characterization of their frequency, pathogenicity and AAO. Importantly, 226 variants met eligibility criteria for inclusion in disease-modifying clinical trials. Furthermore, we demonstrated the predictive value of mean variant AAO and parental AAO in predicting symptomatic AAO, validated against converters who became symptomatic during follow-up in the DIAN Observational Study. This dataset provides critical insights into the global landscape of ADAD and reveals the genetic and AAO heterogeneity of ADAD variants while refining variant trial eligibility criteria.
Indexed as
Alzheimer DiseaseAgedAge of OnsetAmyloid beta-Protein PrecursorFemaleGenetic VariationHumansMaleMiddle AgedMutationPresenilin-1Presenilin-2Amyloid beta-Protein PrecursorAPP protein, humanPresenilin-1Presenilin-2PSEN1 protein, humanPSEN2 protein, humanamyloid precursor proteinpathogenicitypresenilin-1presenilin-2prevalence
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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.