Authors: Weller, Roy; Nicoll, James

Source: Neurological Research, Volume 25, Number 6, September 2003 , pp. 611-616(6)

Publisher: Maney Publishing

Abstract:

Cerebral amyloid angiopathy (CAA) is a feature of ageing and Alzheimer's disease (AD); it is also associated with intracerebral hemorrhage and stroke. Here, the pathogenesis of CAA and its effects on the brain are reviewed and the possible effects of CAA on therapies for Alzheimer's disease are evaluated. Tracer experiments in animals and observations on human brains suggest that peptides such as Aβ are eliminated along the peri-arterial interstitial fluid drainage pathways that are effectively the lymphatics of the brain. In CAA, Aβ becomes entrapped in drainage pathways in the walls of cerebral arteries, reflecting a failure of elimination of Aβ from the ageing brain. One consequence of failure in clearance of Aβ is accumulation of soluble and insoluble Aβ associated with cognitive decline in AD. Replacement of vascular smooth muscle cells by Aβ occurs in severe CAA with weakening of artery walls and increased risk of vessel rupture and intracerebral hemorrhage. Risk factors for CAA include mutations of the amyloid precursor protein (APP) gene and possession of the ε4 allele of apolipoprotein E. There is also evidence that cerebrovascular disease may be a factor in the failure of elimination of Aβ along perivascular pathways in sporadic AD; this would link ageing in cerebral arteries with the pathogenesis of Alzheimer's disease. If therapeutic agents, including anti-Aβ antibodies, are to be used to eliminate Aβ in the treatment of Alzheimer's disease, the effects of CAA on the treatment and the effects of the treatment on the CAA need to be considered.

Keywords: CEREBRAL AMYLOID ANGIOPATHY; STROKE; CEREBROSPINAL FLUID; CEREBRAL HEMORRHAGE; INTERSTITIAL FLUID; ALZHEIMER'S DISEASE; PERIVASCULAR SPACES

Document Type: Research Article

DOI: http://dx.doi.org/10.1179/016164103101202057

Affiliations: Neuropathology, Division of Clinical Neurosciences, University of Southampton School of Medicine, Southampton, UK

Publication date: 2003-09-01

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