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

Hawkes, McLaurin (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 (Digital Object Identifier) Link: https://doi.org/10.1073/pnas.0805453106
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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.

Item Type: Journal Item
Copyright Holders: 2009 The National Academy of Sciences of the USA
ISSN: 1091-6490
Academic Unit/School: Other Departments > Other Departments
Related URLs:
Item ID: 44096
Depositing User: Cheryl Hawkes
Date Deposited: 08 Sep 2015 08:57
Last Modified: 04 Oct 2016 11:48
URI: http://oro.open.ac.uk/id/eprint/44096
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