Inhibition of amyloid-beta-induced neurotoxicity and apoptosis by moderate ethanol preconditioning

Neuroreport. 2004 Sep 15;15(13):2093-6. doi: 10.1097/00001756-200409150-00019.


Consumers of moderate amounts of ethanol have a lower risk of Alzheimer's dementia than do abstainers. In Alzheimer's disease the brain contains many extracellular plaques composed of amyloid-beta (Abeta), a neurotoxic protein linked to pathogenesis of the disease. Here we report that moderate ethanol preconditioning (20-30 mM for 6 days) of organotypic hippocampal-entorhinal slice cultures prevents Abeta-induced neurotoxicity and apoptosis as measured by media lactate dehydrogenase levels and staining with propidium iodide and Hoechst 33342. With Abeta, as with our previous studies of the neurotoxic HIV-1 protein gp120, moderate ethanol preconditioning may interfere with various glial-mediated neurotoxic responses in the slices to Abeta. In addition, we found that moderate ethanol preconditioning causes an almost 3-fold increase in brain levels of heat shock protein 70 (hsp70), a protective molecular chaperone. Our results suggest possible molecular mechanisms underlying the protective effect of moderate drinking against Alzheimer's dementia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects*
  • Benzimidazoles
  • Central Nervous System Depressants / pharmacology*
  • Central Nervous System Depressants / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme-Linked Immunosorbent Assay / methods
  • Ethanol / pharmacology*
  • Ethanol / therapeutic use
  • HSP70 Heat-Shock Proteins / metabolism
  • Hippocampus / drug effects*
  • Hydro-Lyases / metabolism
  • Nerve Degeneration / etiology
  • Nerve Degeneration / prevention & control*
  • Organ Culture Techniques
  • Propidium
  • Rats
  • Rats, Sprague-Dawley


  • Amyloid beta-Peptides
  • Benzimidazoles
  • Central Nervous System Depressants
  • HSP70 Heat-Shock Proteins
  • Propidium
  • Ethanol
  • Hydro-Lyases
  • lactate dehydratase
  • bisbenzimide ethoxide trihydrochloride