title: [Blood-brain barrier and Alzheimer's disease].
abstract: Alzheimer's disease (AD) is the most common cause of dementia, and its pathological hallmarks are senile plaques and neurofibrillary tangles in the brain, which eventually induce neuronal death. The prevailing hypothesis for the pathomechanism of AD is the amyloid cascade hypthesis: amyloid-β peptide (Aβ) deposition in the brain initiates a sequence of events leading to dementia. The blood-brain barrier (BBB) is crucial for AD pathomechanism because the transport of Aβ across the BBB is regulated by the receptor for advanced glycation end products, low-density lipoprotein receptor-related proteins, and the P-glycoprotein. Many studies have elucidated that these transport proteins are impaired in AD patients. Moreover, it is now widely recognized that most cases of AD show vascular pathology. Vascular risk factors such as diabetes mellitus, hypertension, hypercholesterolemia, and obesity are risk factors for AD. Recently, the vascular hypothesis for AD pathomechanism has been proposed; vascular risk factors first lead to BBB dysfunction and oligaemia and then induce Aβ deposition, toxic accumulates, and capillary hypoperfusion in the brain, ultimately leading to neuronal dysfunction. Therapeutic strategies for Aβ clearance from the brain to blood across the BBB have been increasingly developed. The "peripheral sink" approaches are now challenged by anti-Aβ antibodies, the agents with high affinity to Aβ, and the modification of molecules that influence the Aβ transport across the BBB. This review highlights the roles of the BBB in AD pathomechanism and its importance in designing therapeutic strategies.
authors: Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Hiroya
authors: H
authors: Kuwahara
authors: Yoichiro
authors: Y
authors: Nishida
authors: Takanori
authors: T
authors: Yokota
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D006801:Humans
chemical_list: D000682:Amyloid; D000906:Antibodies