APP and Alzheimer disease: It is known that amyloid-beta peptide (Aβ) accumulation acts as a core factor among the multifaceted etiology of AD, which is closely associated with the cerebrovascular dysfunctions, especially brain microcirculation disturbance (Bell and Zlokovic, 2009; Yamazaki and Kanekiyo, 2017; Jack et al., 2018; Hampel et al., 2021; Kim et al., 2021).