Exercise modulates APOE expression in brain cortex of female APOE3 and APOE4 targeted replacement mice.

Apolipoprotein E (ApoE) is the main cholesterol carrier of the brain and the ε4 gene variant (APOE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD), increasing risk up to 15-fold. Several studies indicate that APOE4 modulates critical factors for neuronal function, including brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α). Both proteins show exercise-induced upregulation, which is presumed to mediate many of the beneficial effects of physical activity including improved cognition; however, there is variability in results between individuals potentially in-part due to genetic variations including APOE isoform.