Vascular disorder in Alzheimer's disease: role in pathogenesis of dementia and therapeutic targets.
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.
Zlokovic
Berislav V
BV
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. berislav_zlokovic@urmc.rochester.edu
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology*; D000818:Animals; D003704:Dementia / Q000188:drug therapy / Q000473:pathology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D014652:Vascular Diseases / Q000188:drug therapy* / Q000473:pathology*