From this view, the growing body of evidence supporting the beneficial effects of PE against the risk of developing AD can be explained at multiple levels of mechanistic interaction by which training exercise appears to affect the downstream gut microbial ecosystem and upstream neural plasticity, anti-inflammatory signaling pathways, neurotrophin expression, and neurogenesis via the production of myokines such as irisin and BDNF. This evidence concerns the gene FNDC5 and Alzheimer disease.