Molecular links between Alzheimer's disease and diabetes mellitus

Neuroscience. 2013 Oct 10;250:140-50. doi: 10.1016/j.neuroscience.2013.07.009. Epub 2013 Jul 16.

Abstract

Substantial epidemiological evidence shows an increased risk for developing Alzheimer's disease (AD) in people with diabetes. Yet the underlying molecular mechanisms still remain to be elucidated. This article reviews the current studies on common pathological processes of Alzheimer's disease and diabetes with particular focus on potential mechanisms through which diabetes affects the initiation and progression of Alzheimer's disease. Impairment of insulin signaling, inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, APOEε4 and cholesterol appear to be important mediators and are likely to act synergistically in promoting AD pathology.

Keywords: AD; APP; Alzheimer’s disease; Aβ; BACE1; GSK3β; IDE; IGF; NSAID; amyloid β precursor protein; amyloid β protein; diabetes; glycogen synthase kinase 3β; hIAPP; human islet amyloid polypeptide; insulin-degrading enzyme; insulin-like growth factor; molecular links; non-steroidal anti-inflammatory drug; β-site APP-cleaving enzyme 1.

Publication types

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

MeSH terms

  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics*
  • Amyloidogenic Proteins / metabolism
  • Apolipoprotein E4 / genetics
  • Apolipoprotein E4 / physiology
  • Cholesterol / metabolism
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / genetics*
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Inflammation / physiopathology
  • Insulin / physiology
  • Oxidative Stress / physiology
  • Signal Transduction / physiology

Substances

  • Amyloidogenic Proteins
  • Apolipoprotein E4
  • Glycation End Products, Advanced
  • Insulin
  • Cholesterol