{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:17:56Z","timestamp":1793319476064,"version":"4.5.0"},"reference-count":75,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH) Malaysia","award":["NMRR ID-22-00747-NDH"],"award-info":[{"award-number":["NMRR ID-22-00747-NDH"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Background: Early-onset Alzheimer\u2019s disease (EOAD) is primarily inherited in an autosomal dominant pattern, with mutations in the APP, PSEN1, and PSEN2 genes being central contributors. Diagnosing Alzheimer\u2019s poses challenges due to the coexistence of various co-pathologies, and treatment options remain limited for most patients, apart from familial cases linked to specific genetic mutations. While significant research on Alzheimer\u2019s genetics has been conducted in both Asian and Caucasian populations, the specific mutations and their clinical impacts in EOAD are still inadequately explored. This review aims to provide a detailed analysis of commonly reported genetic mutations and associated clinical features in EOAD patients from Asian and Western populations. Methods: Following the PRISMA-ScR guidelines, a systematic database search was conducted for studies published between 2016 and 2023. After screening 491 records, 36 studies from Asian cohorts and 40 from Western cohorts met the inclusion criteria. Results: The analysis revealed 127 unique mutations in the Asian population and 190 in the Western population. About 16.7% of Asian and 21.9% of Western studies covered both familial and sporadic AD, with consistent patterns across groups. Some mutations were shared between the populations and displayed similar clinical features, while others were population-specific. Conclusions: These findings underscore the considerable variability in EOAD mutations and phenotypes, emphasizing the importance of genetic testing in younger patients to enhance diagnostic accuracy and guide treatment strategies effectively.<\/jats:p>","DOI":"10.3390\/genes16030345","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T07:49:57Z","timestamp":1742197797000},"page":"345","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Clinical Significance of Early-Onset Alzheimer\u2019s Mutations in Asian and Western Populations: A Scoping Review"],"prefix":"10.3390","volume":"16","author":[{"given":"Prevathe","family":"Poniah","sequence":"first","affiliation":[{"name":"Inborn Errors of Metabolism and Genetics Unit, Nutrition, Metabolic and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam 41700, Selangor, Malaysia"},{"name":"Clinical Research Centre, Hospital Raja Permaisuri Bainun, Institute for Clinical Research, National Institutes of Health, Ministry of Health Malaysia, Ipoh 30450, Perak, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2380-8171","authenticated-orcid":false,"given":"Aswir","family":"Abdul Rashed","sequence":"additional","affiliation":[{"name":"Nutrition Unit, Nutrition, Metabolic and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Shah Alam 41700, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7542-2922","authenticated-orcid":false,"given":"Julaina","family":"Abdul Jalil","sequence":"additional","affiliation":[{"name":"Inborn Errors of Metabolism and Genetics Unit, Nutrition, Metabolic and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam 41700, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernie Zuraida","family":"Ali","sequence":"additional","affiliation":[{"name":"Inborn Errors of Metabolism and Genetics Unit, Nutrition, Metabolic and Cardiovascular Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam 41700, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","article-title":"The Neuropathological Diagnosis of Alzheimer\u2019s Disease","volume":"14","author":"Deture","year":"2019","journal-title":"Mol. 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