Chaperone-Mediated APOE4 Refolding Enhancement

**Molecular Mechanism and Rationale** The apolipoprotein E4 (APOE4) isoform represents the strongest genetic risk factor for late-onset Alzheimer's disease, carried by approximately 25% of the population and conferring a 3-4 fold increased risk compared to the protective APOE3 variant. The fundamental pathogenic mechanism underlying APOE4's deleterious effects stems from a critical structural vulnerability: an aberrant domain interaction between the N-terminal (residues 1-165) and C-terminal (r...