Capillary and arterial cerebral amyloid angiopathy in Alzheimer's disease: defining the perivascular route for the elimination of amyloid ? from the human brain

Preston, S.D., Steart, P.V., Wilkinson, A., Nicoll, J.A.R. and Weller, R.O. (2003) Capillary and arterial cerebral amyloid angiopathy in Alzheimer's disease: defining the perivascular route for the elimination of amyloid ? from the human brain. Neuropathology & Applied Neurobiology, 29 (2), 106-117. (doi:10.1046/j.1365-2990.2003.00424.x).

Abstract

Accumulation of amyloid ? (A?) in the extracellular spaces of the cerebral cortex and in blood vessel walls as cerebral amyloid angiopathy is a characteristic of Alzheimer's disease (AD) and the ageing human brain. Studies in animals suggest that A? is eliminated from the brain either directly into the blood or along perivascular interstitial fluid drainage channels. The aim of the present study is to define the perivascular route for the drainage of A? from the human brain. Smears and paraffin sections of post-mortem cortical tissue from 17 cases of AD and from two controls were stained with thioflavin and for A? by immunohistochemistry. Histology and confocal microscopy showed that deposits of A? in the cortical parenchyma were continuous with A? in capillary walls but A? in artery walls was not in continuity with A? in brain parenchyma. Quantitative studies supported these observations. The results of this study suggest that when A? is eliminated from the extracellular spaces of the human brain by the perivascular route, it enters pericapillary spaces and from there drains along the walls of cortical arteries to leptomeningeal arteries. Factors such as overproduction of A?, entrapment of A? in drainage pathways and poor drainage of A? due to functional changes in ageing arteries might result in the failure of elimination of A? from the ageing brain and play a major role in the pathogenesis of AD. Such factors might affect therapies for AD that entail administration of anti-A? antibodies to eliminate A? from the human brain.

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Contributors

Author: J.A.R. Nicoll

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