The genetics of Alzheimer's disease (AD) involve both early-onset familial (EO-FAD) and late-onset (LOAD) forms. EO-FAD is typically caused by rare mutations in three genes: APP, PSEN1, and PSEN2, which lead to early-onset AD. These mutations are fully penetrant and follow an autosomal dominant pattern. The discovery of these genes was pivotal in understanding the molecular mechanisms of AD, including the role of amyloid-beta (Aβ) production and the amyloid cascade hypothesis. The APOE gene, particularly the ε4 allele, is a major genetic risk factor for LOAD, influencing AD risk in a dose-dependent manner. Other genes, such as CD33, CLU, PICALM, and CR1, have been identified through genome-wide association studies (GWASs) as contributing to AD risk. These genes are involved in various pathways, including Aβ production, clearance, lipid metabolism, and innate immunity. GWASs have identified additional AD risk genes, including CD33, GWA_14q31.2, ATXN1, CLU, PICALM, CR1, BIN1, ABCA7, MS4A6A/MS4A4E, CD2AP, and EPHA1. However, the heritability of AD remains largely unexplained, with up to 50% of the genetic variance not accounted for by known genes. Rare variants, such as those in ADAM10, have also been identified, which may contribute to AD risk. These findings highlight the complexity of AD genetics and the need for further research to uncover additional genetic factors and mechanisms underlying the disease. Genetic studies continue to provide insights into the pathogenesis of AD, which are crucial for developing novel therapeutic strategies for prevention and treatment.The genetics of Alzheimer's disease (AD) involve both early-onset familial (EO-FAD) and late-onset (LOAD) forms. EO-FAD is typically caused by rare mutations in three genes: APP, PSEN1, and PSEN2, which lead to early-onset AD. These mutations are fully penetrant and follow an autosomal dominant pattern. The discovery of these genes was pivotal in understanding the molecular mechanisms of AD, including the role of amyloid-beta (Aβ) production and the amyloid cascade hypothesis. The APOE gene, particularly the ε4 allele, is a major genetic risk factor for LOAD, influencing AD risk in a dose-dependent manner. Other genes, such as CD33, CLU, PICALM, and CR1, have been identified through genome-wide association studies (GWASs) as contributing to AD risk. These genes are involved in various pathways, including Aβ production, clearance, lipid metabolism, and innate immunity. GWASs have identified additional AD risk genes, including CD33, GWA_14q31.2, ATXN1, CLU, PICALM, CR1, BIN1, ABCA7, MS4A6A/MS4A4E, CD2AP, and EPHA1. However, the heritability of AD remains largely unexplained, with up to 50% of the genetic variance not accounted for by known genes. Rare variants, such as those in ADAM10, have also been identified, which may contribute to AD risk. These findings highlight the complexity of AD genetics and the need for further research to uncover additional genetic factors and mechanisms underlying the disease. Genetic studies continue to provide insights into the pathogenesis of AD, which are crucial for developing novel therapeutic strategies for prevention and treatment.