Proteostasis Enhancement via APOE Chaperone Targeting

**Background and Rationale** The apolipoprotein E epsilon 4 allele (APOE4) represents the strongest genetic risk factor for late-onset Alzheimer's disease, increasing risk 3-fold in heterozygotes and 8-15-fold in homozygotes. While traditional research has focused on APOE4's effects on amyloid-β clearance and lipid transport, emerging evidence suggests that the structural instability of APOE4 itself creates a fundamental proteostasis crisis that drives neurodegeneration through multiple converg...