Targeting Gut Dysbiosis in APOE4 Carriers: Strategies for Mitigating Alzheimer's Disease Risk

Apolipoprotein E epsilon 4 (APOE4) is the primary genetic risk factor for late-onset Alzheimer's disease (AD). APOE4 carriers, especially females, tend to develop gut dysbiosis earlier than non-carriers, which may elevate their AD risk. Early intervention to address this dysbiosis is critical for risk mitigation. In this presentation, I will show that dysbiosis from AD donors significantly exacerbates AD pathology in young, healthy APOE4 mice, while a healthy donor’s microbiome may provide protective benefits against AD. I will also present data indicating that a prebiotic diet can protect brain metabolism and reduce neuroinflammation in these mice. Furthermore, I will discuss the development of precision probiotics tailored to combat gut dysbiosis in female APOE4 carriers.