Alzheimer's disease and insulin resistance: translating basic science into clinical applications

J Clin Invest. 2013 Feb;123(2):531-9. doi: 10.1172/JCI64595. Epub 2013 Feb 1.


Alzheimer's disease (AD) and diabetes are currently considered among the top threats to human health worldwide. Intriguingly, a connection between these diseases has been established during the past decade, since insulin resistance, a hallmark of type 2 diabetes, also develops in Alzheimer brains. In this article, the molecular and cellular mechanisms underlying defective brain insulin signaling in AD are discussed, with emphasis on evidence that Alzheimer's and diabetes share common inflammatory signaling pathways. I put forward here a hypothesis on how a cross-talk between peripheral tissues and the brain might influence the development of AD, and highlight important unanswered questions in the field. Furthermore, I discuss a rational basis for the use of antidiabetic agents as novel and potentially effective therapeutics in AD.

Publication types

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

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / etiology*
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / physiology
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Brain / drug effects
  • Brain / physiopathology
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / physiopathology
  • Humans
  • Insulin Receptor Substrate Proteins / physiology
  • Insulin Resistance / physiology*
  • Insulin-Like Growth Factor I / physiology
  • Models, Neurological
  • Neurotoxins / metabolism
  • Neurotoxins / toxicity
  • Oxidative Stress
  • Receptor, Insulin / drug effects
  • Receptor, Insulin / physiology
  • Signal Transduction / drug effects
  • Translational Research, Biomedical


  • Amyloid beta-Peptides
  • Insulin Receptor Substrate Proteins
  • Neurotoxins
  • Insulin-Like Growth Factor I
  • Receptor, Insulin