This review summarizes the genetic risk factors for late-onset Alzheimer's disease (AD) and their role in disease pathogenesis. Recent advances in genome-wide association studies (GWAS) have identified several genes associated with AD risk, including ABCA7, BIN1, CASS4, CD33, CD2AP, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB5-DBR1, INPP5D, MS4A, MEF2C, NME8, PICALM, PTK2B, SLC24H4, RIN3, SORL1, and ZCWPW1. Additionally, coding variants such as PLD3 and TREM2 have been identified through genome-wide and sequencing studies. These genes are linked to cellular and neuropathological features of AD, including amyloid-beta (Aβ) production and clearance, neuroinflammation, and endocytosis. Understanding the mechanisms underlying these genetic associations is crucial for developing therapeutic targets. The APOE gene is the strongest risk factor for late-onset AD, with the ε4 allele increasing AD risk. APOE influences Aβ clearance and is involved in lipid metabolism and neuroinflammation. Clusterin (CLU) is also associated with AD, influencing Aβ aggregation and neuroinflammation. ABCA7 is involved in lipid transport and Aβ clearance, while TREM2 is a receptor on microglia that regulates phagocytosis and inflammation. Genetic variants in TREM2, such as R47H, are associated with increased AD risk. Genes involved in endocytosis, such as BIN1, PICALM, CD2AP, and EPHA1, are also linked to AD pathogenesis. These genes influence APP processing, synaptic function, and neuroinflammation. The identification of these genes and their associated pathways provides insights into the complex interplay between genetic susceptibility and molecular mechanisms in AD. Future research aims to integrate genetic, expression, and epigenetic data to better understand AD pathogenesis and develop targeted therapies.This review summarizes the genetic risk factors for late-onset Alzheimer's disease (AD) and their role in disease pathogenesis. Recent advances in genome-wide association studies (GWAS) have identified several genes associated with AD risk, including ABCA7, BIN1, CASS4, CD33, CD2AP, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB5-DBR1, INPP5D, MS4A, MEF2C, NME8, PICALM, PTK2B, SLC24H4, RIN3, SORL1, and ZCWPW1. Additionally, coding variants such as PLD3 and TREM2 have been identified through genome-wide and sequencing studies. These genes are linked to cellular and neuropathological features of AD, including amyloid-beta (Aβ) production and clearance, neuroinflammation, and endocytosis. Understanding the mechanisms underlying these genetic associations is crucial for developing therapeutic targets. The APOE gene is the strongest risk factor for late-onset AD, with the ε4 allele increasing AD risk. APOE influences Aβ clearance and is involved in lipid metabolism and neuroinflammation. Clusterin (CLU) is also associated with AD, influencing Aβ aggregation and neuroinflammation. ABCA7 is involved in lipid transport and Aβ clearance, while TREM2 is a receptor on microglia that regulates phagocytosis and inflammation. Genetic variants in TREM2, such as R47H, are associated with increased AD risk. Genes involved in endocytosis, such as BIN1, PICALM, CD2AP, and EPHA1, are also linked to AD pathogenesis. These genes influence APP processing, synaptic function, and neuroinflammation. The identification of these genes and their associated pathways provides insights into the complex interplay between genetic susceptibility and molecular mechanisms in AD. Future research aims to integrate genetic, expression, and epigenetic data to better understand AD pathogenesis and develop targeted therapies.