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

Selective targeting of perivascular macrophages for clearance of B-amyloid in cerebral amyloid angiopathy
Selective targeting of perivascular macrophages for clearance of B-amyloid in cerebral amyloid angiopathy
Cerebral amyloid angiopathy (CAA), the deposition of beta-amyloid (Abeta) 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 Abeta 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 Abeta(42) 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.

0027-8424
1261-1266
Hawkes, C.A.
88f4a99a-625c-4c6e-a295-09dd67f8afe8
McLaurin, J.
196bc965-5bf0-4168-8963-15afe2170798
Hawkes, C.A.
88f4a99a-625c-4c6e-a295-09dd67f8afe8
McLaurin, J.
196bc965-5bf0-4168-8963-15afe2170798

Hawkes, C.A. and McLaurin, J. (2009) Selective targeting of perivascular macrophages for clearance of B-amyloid in cerebral amyloid angiopathy. Proceedings of the National Academy of Sciences, 106 (4), 1261-1266. (doi:10.1073/pnas.0805453106). (PMID:19164591)

Record type: Article

Abstract

Cerebral amyloid angiopathy (CAA), the deposition of beta-amyloid (Abeta) 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 Abeta 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 Abeta(42) 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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Published date: 21 January 2009
Organisations: Faculty of Medicine

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Local EPrints ID: 353197
URI: https://eprints.soton.ac.uk/id/eprint/353197
ISSN: 0027-8424
PURE UUID: b1e99070-1918-4caf-a442-ccb56ff03066

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Date deposited: 03 Jun 2013 13:13
Last modified: 18 Jul 2017 04:07

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Author: C.A. Hawkes
Author: J. McLaurin

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