Hepatic expression of APOE3 Christchurch mitigates APOE4-related Alzheimer's disease pathologies in mice.

Hepatic expression of APOE3 Christchurch reduces amyloid-β burden and AD pathologies in APOE4-expressing APP/PS1 mice.

• Why it matters: APOE4 is the strongest genetic risk factor for sporadic Alzheimer's disease and worsens AD-related pathologies, making mitigation strategies crucial.
• What they did: Researchers delivered APOE3 Christchurch or APOE3 into the liver via adeno-associated virus in APP/PS1 mice expressing human APOE4, then assessed AD-related outcomes.
• The result: Hepatic APOE3Ch delivery decreased brain amyloid-β, neuroinflammation, neurodegeneration, and cognitive impairments, suggesting liver-targeted gene transfer as a potential therapy for APOE4-associated AD.