Insulin-resistant brain state: the culprit in sporadic Alzheimer's disease?

Ageing Res Rev. 2011 Apr;10(2):264-73. doi: 10.1016/j.arr.2011.01.001. Epub 2011 Jan 22.


Severe abnormalities in brain glucose/energy metabolism and insulin signaling have been documented to take a pivotal role in early sporadic Alzheimer's disease (sAD) pathology. Indeed, the "insulin-resistant brain state" has been hypothesized to form the core of the neurodegenerative events that occur in sAD. In this vein, intracerebroventricular administration of subdiabetogenic doses of streptozotocin (STZ) in rats can induce an insulin-resistant brain state, which is proposed as a suitable experimental model of sAD. This review highlights the involvement of disturbed brain insulin metabolism in sAD etiopathogenesis. Furthermore, current knowledge demonstrates that central STZ administration produces brain pathology and behavioral changes that resemble changes found in sAD patients. The STZ-intracerebroventricularly treated rat represents a promising experimental tool in this field by providing new insights concerning early brain alterations in sAD, which can be translated in novel etiopathogenic and therapeutic approaches in this disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism*
  • Animals
  • Blood Glucose / metabolism*
  • Brain / drug effects
  • Brain / metabolism*
  • Diabetes Mellitus, Experimental / chemically induced*
  • Diabetes Mellitus, Experimental / metabolism
  • Energy Metabolism / drug effects
  • Injections, Intraventricular
  • Insulin / metabolism*
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Streptozocin / administration & dosage*
  • Streptozocin / metabolism


  • Blood Glucose
  • Insulin
  • Streptozocin