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

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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Selective targeting of perivascular macrophages for clearance of β-amyloid in cerebral amyloid angiopathy. / Hawkes, Cheryl A.; McLaurin, Joanne.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 4, 27.01.2009, p. 1261-1266.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Hawkes, CA & McLaurin, J 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, vol. 106, no. 4, pp. 1261-1266. https://doi.org/10.1073/pnas.0805453106

APA

Hawkes, C. A., & McLaurin, J. (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), 1261-1266. https://doi.org/10.1073/pnas.0805453106

Vancouver

Hawkes CA, McLaurin J. 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. 2009 Jan 27;106(4):1261-1266. Epub 2009 Jan 21. doi: 10.1073/pnas.0805453106

Author

Hawkes, Cheryl A. ; McLaurin, Joanne. / Selective targeting of perivascular macrophages for clearance of β-amyloid in cerebral amyloid angiopathy. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 4. pp. 1261-1266.

Bibtex

@article{cedf193bfbf54c5a976a4ecab3c05390,
title = "Selective targeting of perivascular macrophages for clearance of β-amyloid in cerebral amyloid angiopathy",
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.",
author = "Hawkes, {Cheryl A.} and Joanne McLaurin",
year = "2009",
month = jan,
day = "27",
doi = "10.1073/pnas.0805453106",
language = "English",
volume = "106",
pages = "1261--1266",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "4",

}

RIS

TY - JOUR

T1 - Selective targeting of perivascular macrophages for clearance of β-amyloid in cerebral amyloid angiopathy

AU - Hawkes, Cheryl A.

AU - McLaurin, Joanne

PY - 2009/1/27

Y1 - 2009/1/27

N2 - 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.

AB - 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.

U2 - 10.1073/pnas.0805453106

DO - 10.1073/pnas.0805453106

M3 - Journal article

C2 - 19164591

AN - SCOPUS:59049104731

VL - 106

SP - 1261

EP - 1266

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 4

ER -