Presenilin1 FAD mutants and γ‐secretase inhibitors decrease VEGFR2 signaling and block angiogenic functions of brain endothelial cells

Alzheimer’s disease (AD) is a multifactorial and progressive neurodegenerative disease where cerebrovascular abnormalities are commonly observed. Various factors, including decreased sprouting angiogenesis, can cause a reduction in capillary density observed in AD. In addition, brain vascular alterations occur before the appearance of neuropathology in animal AD models. Brain angiogenesis is a reparative function in response to toxic insults and is regulated by endothelial cells (ECs) and angiogenic factors such as the VEGF; impairment in this function would render the brain vulnerable to insults. In present study, we examine the effects of Presenilin 1 (PS1)‐Familial AD (FAD) mutants and γ‐secretase in the VEGF‐induced angiogenic signaling and functions of brain ECs.