Starvation triggers Aβ42 generation from human umbilical vascular endothelial cells

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 A beta(42) under starvation. Starvation can increase the secretion of A beta(42) by altering the expression of beta-secretases (BACE1) and gamma-secretases (APH and PEN2). This process is regulated by macroautophagy. Suppression of macroautophagy induction by 3MA further increased the level of A beta(42) produced under starvation in HUVECs. These results suggest that starvation-induced A beta(42) secretion might contribute to the formation of CAA and hence vascular degeneration in AD. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.