Selective targeting of perivascular macrophages for clearance of β-amyloid in cerebral amyloid angiopathy

Hawkes, Cheryl and McLaurin, JoAnne (2009). Selective targeting of perivascular macrophages for clearance of β-amyloid in cerebral amyloid angiopathy. Proceedings of the National Academy of Sciences of the United States of America, 106(4) pp. 1261–1266.

DOI: https://doi.org/10.1073/pnas.0805453106

Abstract

Cerebral amyloid angiopathy (CAA), the deposition of β-amyloid (Aβ) peptides in leptomeningeal and cortical blood vessels, affects the majority of patients with Alzheimer’s disease (AD). Evidence suggests that vascular amyloid deposits may result from impaired clearance of neuronal Aβ along perivascular spaces. We investigated the role of perivascular macrophages in regulating CAA severity in the TgCRND8 mouse model of AD. Depletion of perivascular macrophages significantly increased the number of thioflavin S-positive cortical blood vessels. ELISA confirmed that this increase was underscored by elevations in total vascular Aβ42 levels. Conversely, stimulation of perivascular macrophage turnover reduced cerebral CAA load, an effect that was not mediated through clearance by microglia or astrocytes. These results highlight a function for the physiological role of perivascular macrophages in the regulation of CAA and suggest that selective targeting of perivascular macrophage activation might constitute a therapeutic strategy to clear vascular amyloid.

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