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

Hepatic expression of APOE3 Christchurch reduces amyloid-β burden by 40% and alleviates AD-related pathologies in APOE4-expressing mice.

• Why it matters: APOE4 significantly increases the risk and severity of Alzheimer's disease, but effective strategies to counteract its effects are lacking, highlighting a critical need for targeted interventions.
• What they did: Researchers used adeno-associated virus to deliver APOE3 Christchurch or APOE3 into the livers of APP/PS1 mice expressing human APOE4, assessing impacts on AD pathology and immune responses.
• The result: Hepatic APOE3Ch expression decreased brain amyloid-β, neuroinflammation, and neurodegeneration, improving cognitive function, and suggesting liver-targeted gene therapy as a promising approach for APOE4-related AD.