If exercise induces the release of EVs containing proteins such as HSP70; BDNF; irisin; CTSB; anti-inflammatory cytokines, such as IL-10 and meteorin-like protein; and other factors, including metabolites and miRNA, which promote neurogenesis and regulate metabolic function and these EVs can cross the BBB, the mechanism through which exercise provides benefits for neurodegenerative diseases, including AD, may be clear. Here, METRNL is linked to Alzheimer disease.