Inhibition of amyloid-β-induced cell death in human brain pericytes in vitro

Amyloid-β protein (Aβ) deposition in the cerebral vascular walls is one of the key features of Alzheimer’s disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). Aβ1–40 carrying the ‘Dutch’ mutation (HCHWA-D Aβ1–40) induces pronounced degeneration of cultured human brain pericytes. In this study, we aimed to identify inhibitors of Aβ-induced toxicity in human brain pericytes. The toxic effect of HCHWA-D Aβ1–40 on human brain pericytes was inhibited by co-incubation with catalase, but not with superoxide dismutase, glutathione or vitamin E analogue Trolox. Catalase interacts with Aβ, both in cell cultures and in cell-free assays, and has a prominent effect on the amount and conformational state of Aβ binding to the cell surface of human brain pericytes. This activity of catalase is likely based on its ability to bind and slowly degrade Aβ and not by its usual capacity to convert hydrogen peroxide. Our data confirm that assembly of Aβ at the cell surface of human brain pericytes is a crucial step in Aβ-induced cellular degeneration of human brain pericytes. Inhibition of fibril formation at the cell surface could be an important factor in therapy aimed at reducing cerebral amyloid angiopathy. [Copyright &y& Elsevier]