Neurovascular function in Alzheimer's disease patients and experimental models

J Cereb Blood Flow Metab. 2011 Jun;31(6):1354-70. doi: 10.1038/jcbfm.2011.43. Epub 2011 Apr 6.

Abstract

The ability of the brain to locally augment glucose delivery and blood flow during neuronal activation, termed neurometabolic and neurovascular coupling, respectively, is compromised in Alzheimer's disease (AD). Since perfusion deficits may hasten clinical deterioration and have been correlated with negative treatment outcome, strategies to improve the cerebral circulation should form an integral element of AD therapeutic efforts. These efforts have yielded several experimental models, some of which constitute AD models proper, others which specifically recapture the AD cerebrovascular pathology, characterized by anatomical alterations in brain vessel structure, as well as molecular changes within vascular smooth muscle cells and endothelial cells forming the blood-brain barrier. The following paper will present the elements of AD neurovascular dysfunction and review the in vitro and in vivo model systems that have served to deepen our understanding of it. It will also critically evaluate selected groups of compounds, the FDA-approved cholinesterase inhibitors and thiazolidinediones, for their ability to correct neurovascular dysfunction in AD patients and models. These and several others are emerging as compounds with pleiotropic actions that may positively impact dysfunctional cerebrovascular, glial, and neuronal networks in AD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Brain / blood supply*
  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology*
  • Cerebrovascular Circulation
  • Cholinesterase Inhibitors / therapeutic use
  • Disease Models, Animal
  • Humans
  • PPAR gamma / agonists
  • Transforming Growth Factor beta / metabolism

Substances

  • Amyloid beta-Protein Precursor
  • Cholinesterase Inhibitors
  • PPAR gamma
  • Transforming Growth Factor beta