Table 1.

Overview of approaches for targeting apolipoprotein E (apoE) for Alzheimer’s disease (AD).

Approach	Rationale	Institution/Company	Risks/Gaps
Bexarotene (RXR agonist; cancer drug-Targetin).	Increase lipidation of apoE.	Indiana University/ADDF [19].	Safety issues due to RXR agonist and impaired brain exposure [52].
Abca1 peptide agonist (derived from carboxy-terminal of apoE).	Increase lipidation of astrocytic apoE4.	Tel Aviv University/Artery Therapeutics [53].	Unclear mechanism by which the peptide agonist activates Abca1, a transmembrane protein.
ApoE4 structure correctors.	Convert neuronal apoE4 to apoE3-like molecule. Mitigate neuronal toxicity caused by apoE4 fragments.	Gladstone Institute/E-Scape bio [54,55].	Based on the premise that neurons express apoE. Effect on astrocytic apoE or apoE lipidation unknown.
ApoE antibody.	Target unlipidated apoE associated with amyloid plaques. Increase amyloid clearance.	Washington University/Denali therapeutics [56].	Based on the premise that unlipidated apoE in associated with plaques. Amount or origin of unlipidated apoE in the brain unknown.
ApoE anti-sense oligonucleotide.	Reduce expression of apoE4 in the CNS.	Washington University/Ionis [57].	Based on the premise that apoE4 is toxic. Safety needs to be assessed as effect of chronic knockdown of apoE4 is not known.