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

Sónia C. Correia, Renato X. Santos, George Perry, Xiongwei Zhu*, Paula I. Moreira, Mark A. Smith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

142 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)264-273
Number of pages10
JournalAgeing Research Reviews
Issue number2
Early online date22 Jan 2011
Publication statusPublished - Apr 2011


  • Alzheimer's disease
  • Glucose metabolism
  • Insulin signaling
  • Streptozotocin

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