The University of Southampton
University of Southampton Institutional Repository

Cerebral Amyloid Angiopathy in the Aetiology of Alzheimer’s disease and its effect on Therapy.

Record type: Article

Amyloid is deposited in the walls of arteries and capillaries as cerebral amyloid angiopathy (CAA) in the brains of older individuals and of those with Alzheimer disease (AD). CAA in AD reflects an age-related failure of elimination of amyloid-beta (A?) from the brain along perivascular lymphatic drainage pathways. In the absence of conventional lymphatic vessel in the brain, interstitial fluid and solutes drain from the brain to cervical lymph nodes along narrow basement membranes in the walls of capillaries and arteries, a pathway that is largely separate from the cerebrospinal fluid. In this review we focus on the pathology and pathogenesis of CAA, its role in the aetiology of AD and its impact on immunotherapy for AD. The motive force for lymphatic drainage of the brain appears to be generated by arterial pulsations. Failure of elimination of A? along perivascular pathways coincides with a reduction in enzymic degradation of A?, reduced absorption of A? into the blood and age-related stiffening of artery walls that appears to reduce the motive force for lymphatic drainage. Reduced clearances of A? and CAA are associated with the accumulation of insoluble and soluble A?s in the brain in AD and the probable loss of homeostasis of the neuronal environment due to retention of soluble metabolites within the brain. Tau metabolism may also be affected. Immunotherapy has been successful in removing insoluble plaques of A? from the brain in AD but with little effect on cognitive decline. One major problem is the increase in CAA in immunised patients that probably prevents the complete removal of A? from the brain. Increased knowledge of the physiology and structural and genetic aspects of the lymphatic drainage of A? from the brain will stimulate the development of therapeutic strategies for the prevention and treatment of AD

PDF 8524941962858360_article.pdf - Other
Restricted to Repository staff only
Download (2MB)
PDF 8524941962858360_article.pdf - Accepted Manuscript
Restricted to Repository staff only
Download (2MB)

Citation

Carare, Roxana-Octavia, Preston, S.D., Subash, M. and Weller, R.O. (2009) Cerebral Amyloid Angiopathy in the Aetiology of Alzheimer’s disease and its effect on Therapy. Alzheimer's Research & Therapy, 1, (2) (doi:10.1186/alzrt6).

More information

Published date: 12 October 2009

Identifiers

Local EPrints ID: 142285
URI: http://eprints.soton.ac.uk/id/eprint/142285
ISSN: 1758-9193
PURE UUID: bbef6d89-dd71-4677-aa8a-45f06c59ba3e

Catalogue record

Date deposited: 01 Apr 2010 09:33
Last modified: 18 Jul 2017 23:12

Export record

Altmetrics

Contributors

Author: S.D. Preston
Author: M. Subash
Author: R.O. Weller

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×