AEE4 Antibody

Introduction to Anti-apoE4 Antibodies

Anti-apoE4 antibodies are monoclonal antibodies (mAbs) designed to target apolipoprotein E4 (apoE4), a genetic variant strongly associated with late-onset Alzheimer’s disease (AD). ApoE4 is the most prevalent genetic risk factor for AD, contributing to amyloid-β (Aβ) plaque accumulation, tau hyperphosphorylation, and neuronal dysfunction . These antibodies aim to counteract apoE4-driven pathologies by selectively binding to its misfolded or aggregated forms, facilitating plaque clearance and mitigating cognitive decline .

Mechanisms of Action

Anti-apoE4 antibodies exert therapeutic effects through multiple pathways:

1. Aβ Plaque Clearance:

   • Bind apoE4 co-deposited with Aβ, promoting microglial phagocytosis and plaque degradation .

   • Example: HAE-4 reduced Aβ burden by 50% in APPPS1-21/APOE4 mice .

2. Tau Pathology Inhibition:

   • Block Aβ-driven tau seeding and spreading, mitigating neuritic dystrophy .

3. Receptor Modulation:

   • Restore apoER2 receptor levels, improving synaptic function .

Preclinical and Clinical Research Findings

Preclinical Studies:

Clinical Trials:

• Lecanemab (BAN2401): Demonstrated 47% slowing of cognitive decline in mild AD patients, with amyloid clearance in 80% of subjects .

• Aducanumab: Reduced Aβ plaques by 93% at high doses but showed dose-dependent amyloid-related imaging abnormalities (ARIA) .

Comparative Analysis of Anti-apoE4 Antibodies

Ongoing Research and Future Directions

• DIAN-TU Trial: Lecanemab is being tested in combination with anti-tau antibody E2814 in familial AD patients (NCT05269394) .

• Subcutaneous Formulations: Lecanemab’s subcutaneous delivery is under Phase 1 evaluation to improve accessibility .

• Biomarker-Driven Trials: Focus on APOE4 carriers and asymptomatic individuals to optimize dosing and efficacy .