Discussion
AD
INFLAMMATION
In this study, we sought to shed light on the molecular mechanisms underlying the beneficial effects of exercise in AD by examining a priori hypothesized molecular effectors in plasma NDEVs from AD patients participating in a RCT of exercise. We found that in patients with mild to moderate AD, 16 weeks of aerobic exercise increased NDEV levels of BDNF, proBDNF, and humanin (Fig. BDNF is a neurotrophin produced upon proteolytic cleavage of its precursor, proBDNF, which is also bioactive. Physical activity increases BDNF concentrations in brain [Humanin is a mitochondria-derived peptide that suppresses neuronal apoptosis, preserves synapses, reduces inflammation, and supports glucose and oxidative metabolism [Exercise-induced factors released from muscle and other organs, collectively coined exerkines, can mediate systemic responses to physical activity [Our study also indicates that neuronal exercise effects are coordinated across multiple inter-connected pathways; this is suggested by the correlation between changes in NDEV BDNF and irisin (Fig. SWe explored whether exercise effects may differ by APOE genotype, as previous studies have shown that, in both healthy elderly and AD individuals, beneficial effects of physical activity on cognition and hippocampal volume are stronger in ε4 carriers [