APP and Alzheimer disease: They found that exercise could modulate various neurotrophic factors (e.g., BDNF) and secretory enzymes (e.g., γ-secretase) that cleave APP through the non-β-amyloid pathway to reduce Aβ aggregation and improve the hippocampal microenvironment, which further promotes the survival, proliferation and differentiation of newborn neuron to enhance AHN and improve cognitive function of AD mouse (Vaynman et al., 2004; Inoue et al., 2015; Yu et al., 2021; Figure 3).