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From the Department of Neuropathology,*
University of
Southampton Medical School, Southampton General Hospital, Southampton,
United Kingdom, and Haldeman Laboratory for Alzheimer Disease
Research,
Sun Health Research Institute, Sun
City, Arizona
Cerebral amyloid angiopathy in Alzheimer's disease is characterized by deposition of amyloid ß (Aß) in cortical and leptomeningeal vessel walls. Although it has been suggested that Aß is derived from vascular smooth muscle, deposition of Aß is not seen in larger cerebral vessel walls nor in extracranial vessels. In the present study, we examine evidence for the hypothesis that Aß is deposited in periarterial interstitial fluid drainage pathways of the brain in Alzheimer's disease and that this contributes significantly to cerebral amyloid angiopathy. There is firm evidence in animals for drainage of interstitial fluid from the brain to cervical lymph nodes along periarterial spaces; similar periarterial channels exist in humans. Biochemical study of 6 brains without Alzheimer's disease revealed a pool of soluble Aß in the cortex. Histology and immunocytochemistry of 17 brains with Alzheimer's disease showed that Aß accumulates five times more frequently around arteries than around veins, with selective involvement of smaller arteries. Initial deposits of Aß occur at the periphery of arteries at the site of the putative interstitial fluid drainage pathways. These observations support the hypothesis that Aß is deposited in periarterial interstitial fluid drainage pathways of the brain and contributes significantly to cerebral amyloid angiopathy in Alzheimer's disease.
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