Prevention of amyloid beta-induced memory impairment by fluvastatin, associated with the decrease in amyloid beta accumulation and oxidative stress in amyloid beta injection mouse model

Int J Mol Med. 2008 May;21(5):531-7.

Abstract

Alzheimer's disease (AD), the most common cause of dementia in the elderly, is characterized by amyloid beta (Abeta)-containing plaques and neurofibrillary tangles, and synaptic and neuronal loss, along with progressive cognitive impairment. Although growing evidence suggests the beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) on AD, this notion is still controversial. To evaluate the efficacy of statins for Abeta-induced cognitive impairment, we employed an Abeta injection model. Using this model, the present study demonstrated that pretreatment with fluvastatin, but not post-treatment just after Abeta exposure, prevented Abeta-induced memory impairment. We also observed that fluvastatin significantly decreased Abeta accumulation and oxidative stress after Abeta injection. Mice treated with simvastatin, but not fluvastatin, did not demonstrate the prevention of Abeta-induced memory impairment, and showed no significant decrease in oxidative stress. More importantly, fluvastatin significantly prevented the loss of neurons in the basal forebrain induced by Abeta. Overall, the present study demonstrated that fluvastatin significantly prevented memory impairment induced by Abeta. The beneficial effects of fluvastatin might be explained by the preservation of neurons through a significant decrease in Abeta accumulation and oxidative stress. In clinical practice, the timing of the start of fluvastatin treatment might be critical in achieving a beneficial effect on cognitive function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / complications
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Behavior, Animal / physiology
  • Fatty Acids, Monounsaturated / therapeutic use*
  • Fluvastatin
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Indoles / therapeutic use*
  • Male
  • Memory Disorders / etiology
  • Memory Disorders / pathology
  • Memory Disorders / prevention & control*
  • Mice
  • Oxidative Stress*
  • Simvastatin / therapeutic use

Substances

  • Amyloid beta-Peptides
  • Fatty Acids, Monounsaturated
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indoles
  • Fluvastatin
  • Simvastatin