APP and Cognitive impairment: As a key player in the cognitive impairment of AD (LaFerla et al., 2007), Aβ is produced by sequential enzymatic cleavage of amyloid precursor protein (APP) by β- and γ-secretases (Selkoe, 2001; Ly et al., 2013; Wang et al., 2017, 2019; Zhang S. et al., 2018).