{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:40:23Z","timestamp":1791668423911,"version":"4.3.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"The Dominantly Inherited Alzheimer Network","award":["U19AG032438"],"award-info":[{"award-number":["U19AG032438"]}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"publisher","award":["SG-20-690363-DIAN"],"award-info":[{"award-number":["SG-20-690363-DIAN"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005224","name":"German Center for Neurodegenerative Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005224","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Neurological Research"},{"name":"Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea","award":["RS-2024-00344521"],"award-info":[{"award-number":["RS-2024-00344521"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We present a comprehensive global analysis of genetic variants associated with autosomal-dominant Alzheimer\u2019s 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.<\/jats:p>\n               <jats:p>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.<\/jats:p>","DOI":"10.1093\/brain\/awaf038","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T18:15:11Z","timestamp":1738692911000},"page":"2429-2440","source":"Crossref","is-referenced-by-count":24,"title":["The landscape of autosomal-dominant Alzheimer\u2019s disease: global distribution and age of onset"],"prefix":"10.1093","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3154-8285","authenticated-orcid":false,"given":"Haiyan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W","family":"Marsh","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Shi","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Washington University School of Medicine , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan E","family":"Renton","sequence":"additional","affiliation":[{"name":"Ronald M. Loeb Center for Alzheimer\u2019s Disease, Department of Genetics and Genomic Sciences, and Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M","family":"Bowling","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Ziegemeier","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Washington University School of Medicine , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Cao","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Washington University School of Medicine , St Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisha","family":"Aristel","sequence":"additional","affiliation":[{"name":"Ronald M. 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