Capillary and arterial cerebral amyloid angiopathy in Alzheimer's disease: defining the perivascular route for the elimination of amyloid β 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 β from the human brain. Neuropathology & Applied Neurobiology, 29, (2), 106-117. (doi:10.1046/j.1365-2990.2003.00424.x).
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Accumulation of amyloid β (Aβ) 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 Aβ 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 Aβ 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 Aβ by immunohistochemistry. Histology and confocal microscopy showed that deposits of Aβ in the cortical parenchyma were continuous with Aβ in capillary walls but Aβ in artery walls was not in continuity with Aβ in brain parenchyma. Quantitative studies supported these observations. The results of this study suggest that when Aβ 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 Aβ, entrapment of Aβ in drainage pathways and poor drainage of Aβ due to functional changes in ageing arteries might result in the failure of elimination of Aβ 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-Aβ antibodies to eliminate Aβ from the human brain.
|Subjects:||R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry|
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Clinical Neurosciences
|Date Deposited:||28 Apr 2006|
|Last Modified:||02 Mar 2012 12:05|
|Contributors:||Preston, S.D. (Author)
Steart, P.V. (Author)
Wilkinson, A. (Author)
Nicoll, J.A.R. (Author)
Weller, R.O. (Author)
|Contact Email Address:||firstname.lastname@example.org|
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