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We placed particular emphasis on amyloid\/tau status and assessed gender differences. Multiple polygenic risk scores were computed to capture different aspects of genetic predisposition. We additionally compared AD risk in ALFA to that across the full disease spectrum from the Alzheimer's Disease Neuroimaging Initiative (ADNI).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Results show that the ALFA project has been successful at establishing a cohort of cognitively unimpaired individuals at high genetic predisposition of AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>It is, therefore, well\u2010suited to study early pathophysiological changes in the preclinical AD\u00a0<jats:italic>continuum<\/jats:italic>.<\/jats:p><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Prevalence of \u03b54 carriers in ALzheimer and FAmilies (ALFA) is higher than in the general European population<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The ALFA study is highly enriched in Alzheimer's disease (AD) genetic risk factors beyond <jats:italic>APOE<\/jats:italic><\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>AD genetic profiles in ALFA are similar to clinical groups along the <jats:italic>continuum<\/jats:italic><\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ALFA has succeeded in establishing a cohort of cognitively unimpaired individuals at high genetic AD risk<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ALFA is well suited to study pathogenic events\/early pathophysiological changes in AD<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><\/jats:sec>","DOI":"10.1002\/alz.13537","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T06:30:23Z","timestamp":1702449023000},"page":"1703-1715","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Genetic characterization of the ALFA study: Uncovering genetic profiles in the Alzheimer's 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