Blood-brain barrier dysfunction as a cause and consequence of Alzheimer's disease.
The blood-brain barrier (BBB) plays critical roles in the maintenance of central nervous system (CNS) homeostasis. Dysfunction of the BBB occurs in a number of CNS diseases, including Alzheimer's disease (AD). A prevailing hypothesis in the AD field is the amyloid cascade hypothesis that states that amyloid-β (Aβ) deposition in the CNS initiates a cascade of molecular events that cause neurodegeneration, leading to AD onset and progression. In this review, the participation of the BBB in the amyloid cascade and in other mechanisms of AD neurodegeneration will be discussed. We will specifically focus on three aspects of BBB dysfunction: disruption, perturbation of transporters, and secretion of neurotoxic substances by the BBB. We will also discuss the interaction of the BBB with components of the neurovascular unit in relation to AD and the potential contribution of AD risk factors to aspects of BBB dysfunction. From the results discussed herein, we conclude that BBB dysfunction contributes to AD through a number of mechanisms that could be initiated in the presence or absence of Aβ pathology.
1] GRECC, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA [2] Division of Gerontology and Geriatric Medicine, Department of Internal Medicine, University of Washington School of Medicine, Seattle, Washington, USA [3] Department of Pathology, School of Dental Medicine, University of Pennsylvania, Seattle, Washington, USA.
Michelle A
MA
Erickson
William A
WA
Banks
D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism
D016229:Amyloid beta-Peptides; D027342:Excitatory Amino Acid Transporter 2; D012709:Serum Albumin