FNDC5 and Alzheimer disease: FNDC5/irisin levels in the hippocampus and cerebrospinal fluid of AD patients are significantly reduced; regular aerobic exercise, via PGC-1α upregulation, elevates FNDC5 expression, enhancing irisin-mediated neprilysin (NEP) secretion and ADAM10 activity, synergistically inhibiting BACE1 and accelerating Aβ degradation (Lourenco et al., 2019).