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Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy

Hawkes, Cheryl A.; Härtig, Wolfgang; Kacza, Johannes; Schliebs, Reinhard; Weller, Roy O.; Nicoll, James A. and Carare, Roxana O. (2011). Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy. Acta Neuropathologica, 121(4) pp. 431–443.

DOI (Digital Object Identifier) Link: https://doi.org/10.1007/s00401-011-0801-7
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Abstract

The deposition of amyloid-β (Aβ) peptides in the walls of leptomeningeal and cortical blood vessels as cerebral amyloid angiopathy (CAA) is present in normal ageing and the majority of Alzheimer’s disease (AD) brains. The failure of clearance mechanisms to eliminate Aβ from the brain contributes to the development of sporadic CAA and AD. Here, we investigated the effects of CAA and ageing on the pattern of perivascular drainage of solutes in the brains of naïve mice and in the Tg2576 mouse model of AD. We report that drainage of small molecular weight dextran along cerebrovascular basement membranes is impaired in the hippocampal capillaries and arteries of 22-month-old wild-type mice compared to 3- and 7-month-old animals, which was associated with age-dependent changes in capillary density. Age-related alterations in the levels of laminin, fibronectin and perlecan in vascular basement membranes were also noted in wildtype mice. Furthermore, dextran was observed in the walls of veins of Tg2576 mice in the presence of CAA, suggesting that deposition of Aβ in vessel walls disrupts the normal route of elimination of solutes from the brain parenchyma. These data support the hypothesis that perivascular solute drainage from the brain is altered both in the ageing brain and as a consequence of CAA. These findings have implications for the success of therapeutic strategies for the treatment of AD that rely upon the health of the ageing cerebral vasculature.

Item Type: Journal Item
Copyright Holders: 2011 Springer-Verlag
ISSN: 1432-0533
Keywords: Alzheimer’s disease; amyloid-β; cerebral vasculature; perivascular drainage; basement membranes; cerebral amyloid angiopathy
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
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Item ID: 44093
Depositing User: Cheryl Hawkes
Date Deposited: 07 Sep 2015 10:15
Last Modified: 07 Dec 2018 10:34
URI: http://oro.open.ac.uk/id/eprint/44093
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