Molecular Insight into the Therapeutic Promise of Targeting APOE4 for Alzheimer’s Disease

Table 1

Outline of therapeutic agents for targeting APOE4 for Alzheimer’s disease.

Therapeutic strategies	Principle	Studies		References
		Animal models	Humans
RXR, LXR, PPARγ agonists	Increases the lipidation of APOE and promotes Aβ clearance	Mouse	Yes	[75–90, 91, 98]
Anti-APOE4 monoclonal antibody	Increases amyloid clearance and decreases APOE-associated toxic effects		Yes	[99–102, 122, 196]
Small peptides comprising the receptor-binding region in APOE	Reduces inflammation and neurotoxicity, increases APOE3-linked protective functions	Mouse	No	[123, 132, 133, 197, 198]
Small molecules	Increases Aβ clearance, APOE signaling, and cholesterol transport	Mouse	No	[175, 176]
APOE4 structure correctors (GIND25 and PH002)	Interferes with domain-domain interaction in APOE4 thus reducing its toxic effects		No	[145–147]
Viral-mediated APOE2 expression	Enhances APOE-connected neurodefensive effects	Mouse	Yes	[166, 169, 199]
Aβ12-28P, Aβ20-29 peptide, small-molecule inhibitors	Increases amyloid clearance	Mouse	No	[153–157]
Cyclosporine A	Decreases leakage of blood-derived toxic molecules in APOE4-carrying brain	Mouse	Yes	[179, 200]