APP and Cognitive impairment: Aβ peptides, such as Aβ40, Aβ42, and Aβ43, are the products of the successive cleavage of amyloid precursor protein (APP) by β- and γ-secretases, and they can assemble into insoluble beta-sheet fibrillar aggregates that deposit extracellularly in the brain parenchyma and cerebral vasculature, causing the damage of synaptic structure and function, and neuronal atrophy in the hippocampus area and then spreading to cortical regions, resulting in cognitive impairment and dementia (Lu et al., 2013; Khan et al., 2014).