{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:21:37Z","timestamp":1787793697952,"version":"build-2784847793"},"reference-count":193,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sofia University \u201cSt Kliment Ohridski\u201d Student Council","award":["80-10-154"],"award-info":[{"award-number":["80-10-154"]}]},{"name":"Science Fund of Sofia University \u201cSt Kliment Ohridski\u201d","award":["80-10-154"],"award-info":[{"award-number":["80-10-154"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex neurodegenerative condition which, despite its high prevalence and socioeconomic impact on the world, has an etiology that remains poorly understood. The genetic causes of AD are complex and have been continuously studied for decades. They range from rare pathogenic, highly penetrant mutations in early-onset (EOAD) forms, which account for 5% of the cases to multiple-risk alleles across different genes in late-onset (LOAD) forms. Monogenic causes of EOAD allocate within APP, PSEN1, and PSEN2 genes in 10\u201315% of cases. The most significant risk factor in LOAD heritability is the APOE \u03b54 allele, as well as numerous loci within genes involved in immunity, endocytosis, lipid metabolism, and amyloid and tau processing. LOAD can also be attributed to the accumulation of somatic mutations, which may be detected by analysis of brain-derived cell-free DNA (cfDNA) in plasma. This review offers a comprehensive overview of the genetic architecture of Alzheimer\u2019s disease, with particular focus on the molecular mechanisms underlying both early- and late-onset forms of the condition. An improved understanding of the genetic etiology of AD can aid better prevention, earlier diagnosis, and novel therapeutic approaches. This can be achieved by analyzing understudied populations, performing case-control studies with appropriately matched controls, and surveying brain-derived cell-free DNA in plasma, with the latter having the potential to contribute to the implementation of liquid biopsy in dementology.<\/jats:p>","DOI":"10.3390\/ijms26167819","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T15:53:27Z","timestamp":1755100407000},"page":"7819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Recent Advances and Future Directions in Alzheimer\u2019s Disease Genetic Research"],"prefix":"10.3390","volume":"26","author":[{"given":"Mikaela","family":"Stancheva","sequence":"first","affiliation":[{"name":"Department of Genetics, Faculty of Biology, Sofia University \u201cSt. Kliment Ohridski\u201d, 1164 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2027-6122","authenticated-orcid":false,"given":"Draga","family":"Toncheva","sequence":"additional","affiliation":[{"name":"Bulgarian Academy of Sciences, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6441-629X","authenticated-orcid":false,"given":"Sena","family":"Karachanak-Yankova","sequence":"additional","affiliation":[{"name":"Department of Genetics, Faculty of Biology, Sofia University \u201cSt. Kliment Ohridski\u201d, 1164 Sofia, Bulgaria"},{"name":"Department of Medical Genetics, Medical Faculty, Medical University-Sofia, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1590\/1980-57642020dn14-020001","article-title":"Daily Functioning and Dementia","volume":"14","author":"Cipriani","year":"2020","journal-title":"Dement. 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