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Abstract: Cerebral amyloid angiopathy is a common feature in Alzheimer’s disease (AD), which is characterized by amyloid deposit around brain vessels including capillaries. The origin of the amyloid protein of CAA remains controversial. In our work, we provide data to show that primary umbilical vein endothelial cells (HUVEC) harbor APP processing secretases and can produce Aβ42 under starvation. Starvation can increase the secretion of Aβ42 by altering the expression of β-secretases (BACE1) and γ-secretases (APH and PEN2). This process is regulated by macroautophagy. Suppression of macroautophagy induction by 3MA further increased the level of Aβ42 produced under starvation in HUVECs. These results suggest that starvation-induced Aβ42 secretion might contribute to the formation of CAA and hence vascular degeneration in AD. [Copyright &y& Elsevier]