The apolipoprotein E (APOE) <i>ε</i>4 allele is the primary genetic driver of late-onset Alzheimer's disease (AD), a complex neurodegenerative disorder characterized by the interplay of amyloid-β (Aβ) accumulation, tau pathology, neuroinflammation, and lipid metabolism dysfunction. The gene discussed is APOE; the disease is early-onset autosomal dominant Alzheimer disease.