Research Progress of APOE Gene in Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is the most common type of dementia worldwide, and the apolipoprotein E (APOE) gene is the strongest genetic risk factor associated with AD. APOE gene polymorphism (especially represented by the ε4 allele) significantly increases AD susceptibility through multiple biological pathways, including β-amyloid (Aβ) metabolic disorders, tau protein pathology, neuroinflammation, blood-brain barrier disruption, and impaired synaptic plasticity; the ε2 allele exerts a protective effect [1]. This review systematically analyzes the molecular mechanisms by which APOE regulates AD progression, focuses on clinical translation progress such as the construction of risk prediction models, the discovery of diagnostic biomarkers, and the development of therapeutic targeting strategies, discusses unresolved scientific challenges including the pathogenesis of ε4 non-carriers, gender-specific differences, and epigenetic regulation, and prospects the application potential of cutting-edge technologies such as single-cell sequencing, brain organoids, and artificial intelligence in advancing APOE-related AD mechanism research and therapeutic breakthroughs.