BACE1在脑淀粉样血管病中的作用研究

Objective: A significant cause of spontaneous hemorrhages in the elderly is cerebral amyloid angiopathy (CAA) which causes degeneration of cerebral vessels, however, the mechanisms are unclear. Methods: We isolated leptomeningeal vessels from rapidly autopsied brains (average postmortem intervals 3.28 hours) with 9 cases of CAA and 10 cases of age-matched controls and used molecular, cell biology and immunohistochemical approaches to examine β-site APP cleaving enzyme 1 (BACE1) protein expression and enzymatic activities as well as tight junction molecular components in small and medium-sized arteries of the cerebral cortex and leptomeninges. Results: We not only identified in the cerebral vessels, including leptomeningeal and cortical vessels, but also found a significant elevation of both BACE1 protein levels and enzymatic activities in leptomeningeal vessels from CAA patients. Moreover, overexpression of BACE1 in endothelial cells resulted in a significant reduction of Occludin, a tight junction protein in blood vessels. Conclusion: These findings suggest that in addition to neurons, cerebral vascular cells express functional BACE1. Moreover, elevated vascular BACE1 may contribute to deficiency of Occludin in cerebral vessels, which ultimately plays a critical role in pathogenesis of CAA and its related hemorrhage.