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Failure of perivascular drainage of β-amyloid in cerebral amyloid angiopathy

Hawkes, Cheryl A.; Jayakody, Nimeshi; Johnston, David A.; Bechmann, Ingo and Carare, Roxana O. (2014). Failure of perivascular drainage of β-amyloid in cerebral amyloid angiopathy. Brain Pathology, 24(4) pp. 396–403.

DOI (Digital Object Identifier) Link: https://doi.org/10.1111/bpa.12159
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Abstract

In Alzheimer's disease, amyloid-β (Aβ) accumulates as insoluble plaques in the brain and deposits in blood vessel walls as cerebral amyloid angiopathy (CAA). The severity of CAA correlates with the degree of cognitive decline in dementia. The distribution of Aβ in the walls of capillaries and arteries in CAA suggests that Aβ is deposited in the perivascular pathways by which interstitial fluid drains from the brain. Soluble Aβ from the extracellular spaces of gray matter enters the basement membranes of capillaries and drains along the arterial basement membranes that surround smooth muscle cells toward the leptomeningeal arteries. The motive force for perivascular drainage is derived from arterial pulsations combined with the valve effect of proteins present in the arterial basement membranes. Physical and biochemical changes associated with arteriosclerosis, aging and possession of apolipoprotein E4 genotype lead to a failure of perivascular drainage of soluble proteins, including Aβ. Perivascular cells associated with arteries and the lymphocytes recruited in the perivenous spaces contribute to the clearance of Aβ. The failure of perivascular clearance of Aβ may be a major factor in the accumulation of Aβ in CAA and may have significant implications for the design of therapeutics for the treatment of Alzheimer's disease.

Item Type: Journal Item
Copyright Holders: 2014 International Society of Neuropathology
ISSN: 1750-3639
Keywords: Alzheimer's disease; amyloid β; cerebral amyloid angiopathy; interstitial fluid neuroimmunology; perivascular drainage
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: 44081
Depositing User: Cheryl Hawkes
Date Deposited: 11 Sep 2015 09:36
Last Modified: 07 Dec 2018 10:34
URI: http://oro.open.ac.uk/id/eprint/44081
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