CEREBRAL AMYLOID ANGIOPATHY - AMYLOID-BETA ACCUMULATES IN PUTATIVE INTERSTITIAL FLUID DRAINAGE PATHWAYS IN ALZHEIMERS-DISEASE

Cerebral amyloid angiopathy in Alzheimer's disease is characterized by deposition of amyloid beta (A beta) in cortical and leptomeningeal ve ssel walls. Although it has been suggested that A beta is derived from vascular smooth muscle, deposition of A beta is not seen in. larger c erebral vessel walls nor in extracranial vessels. In the present study , we examine evidence for the hypothesis that A beta is deposited in p eriarterial Interstitial fluid drainage pathways of the brain in Alzhe imer's disease and that this contributes significantly to cerebral amy loid angiopathy, There is firm evidence in animals for drainage of int erstitial fluid from the brain to cervical lymph nodes along periarter ial spaces; similar periarterial channels exist in humans. Biochemical study of 6 brains without Alzheimer's disease revealed a pool of solu ble A beta in the cortex. Histology and immunocytochemistry of 17 brai ns with Alzheimer's disease showed that A beta accumulates five times more frequently around arteries than around veins, with selective invo lvement of smaller arteries. Initial deposits of A beta occur at the p eriphery of arteries at the site of the putative interstitial fluid dr ainage pathways. These observations support the hypothesis that A beta is deposited in periarterial interstitial fluid drainage pathways of the brain and contributes significantly to cerebral amyloid angiopathy in Alzheimer's disease.