Title: Blood-brain barrier dysfunction as a cause and consequence of Alzheimer's disease.
Authors: Erickson, Michelle A; Banks, William A
Published In J Cereb Blood Flow Metab, (2013 Oct)
Abstract: 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.
PubMed ID: 23921899
MeSH Terms: Aging/metabolism; Aging/pathology; Alzheimer Disease/etiology*; Alzheimer Disease/metabolism; Alzheimer Disease/pathology; Amyloid beta-Peptides/blood; Amyloid beta-Peptides/cerebrospinal fluid; Amyloid beta-Peptides/metabolism; Animals; Biological Transport; Blood-Brain Barrier/metabolism*; Blood-Brain Barrier/pathology; Excitatory Amino Acid Transporter 2/metabolism; Humans; Oxidative Stress; Risk Factors; Serum Albumin/metabolism