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Adv Drug Deliv Rev. 2002 Dec 7;54(12):1553-9.

Vascular disorder in Alzheimer's disease: role in pathogenesis of dementia and therapeutic targets.

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Frank P Smith Laboratories for Neurosurgery and Division of Neurovascular Biology, Center for Aging and Developmental Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.


It is not clear whether Alzheimer's Disease (AD) is primarily a neurodegenerative disorder or not. A body of evidence suggests that vascular disorder in brains of individuals with AD contributes to the extremes of this disease. This raises a question whether Alzheimer's dementia is secondary to vascular dysfunction in the central nervous system (CNS) and, therefore, the neurodegeneration that follows is a consequence of inadequate cerebral blood flow, altered brain metabolism and failure in physiological functions of brain endothelium which represents a site at the blood-brain barrier (BBB). In this paper the evidence for a primary role of the CNS vascular system in pathogenesis of Alzheimer's dementia is reviewed to show how alterations in transport across the BBB contribute to development of cerebral beta-amyloidosis in AD. In addition, vascularly-based therapeutic strategies to limit the development of beta-amyloidosis and to remove amyloid and plaques from the CNS of AD individuals are discussed.

[Indexed for MEDLINE]

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