Neurovascular dysfunction and faulty amyloid β-peptide clearance in Alzheimer disease

Cold Spring Harb Perspect Med. 2012 Oct 1;2(10):a011452. doi: 10.1101/cshperspect.a011452.

Abstract

Neurovascular dysfunction is an integral part of Alzheimer disease (AD). Changes in the brain vascular system may contribute in a significant way to the onset and progression of cognitive decline and the development of a chronic neurodegenerative process associated with accumulation of amyloid β-peptide (Aβ) in brain and cerebral vessels in AD individuals and AD animal models. Here, we review the role of the neurovascular unit and molecular mechanisms in cerebral vascular cells behind the pathogenesis of AD. In particular, we focus on blood-brain barrier (BBB) dysfunction, decreased cerebral blood flow, and impaired vascular clearance of Aβ from brain. The data reviewed here support an essential role of the neurovascular and BBB mechanisms in AD pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / physiopathology*
  • Brain / blood supply*
  • Brain / pathology
  • Brain / physiopathology
  • Cerebrovascular Circulation / physiology*
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / metabolism

Substances

  • Amyloid beta-Peptides
  • Glucose Transporter Type 1
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic