Role of insulin resistance in Alzheimer’s disease

Zhiyou Cai, Ming Xiao, Liying Chang, Liang Jun Yan

Research output: Contribution to journalReview article

16 Scopus citations

Abstract

A critical role of insulin resistance (IR) in Alzheimer’s disease (AD) includes beta-amyloid (Aβ) production and accumulation, the formation of neurofibrillary tangles (NFTs), failure of synaptic transmission and neuronal degeneration. Aβ is sequentially cleavaged from APP by two proteolytic enzymes: β-secretase and γ-secretase. IR could regulate Aβ production via enhancing β- and γ-secretase activity. Meanwhile, IR induces oxidative stress and inflammation in the brain which contributes toAβ and tau pathology. Aβ accumulation can enhance IR through Aβ-mediated inflammation and oxidative stress. IR is a possible linking between amyloid plaques and NFTs pathology via oxidative stress and neuroinflammation. Additionally, IR could disrupt acetylcholine activity, and accelerate axon degeneration and failures in axonal transport, and lead to cognitive impairment in AD. Preclinical and clinical studies have supported that insulin could be useful in the treatment of AD. Thus, an effective measure to inhibit IR may be a novel drug target in AD.

Original languageEnglish
Article numberA001
Pages (from-to)839-851
Number of pages13
JournalMetabolic Brain Disease
Volume30
Issue number4
DOIs
StatePublished - 1 Aug 2015

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Keywords

  • Alzheimer’s disease
  • Cognitive impairment
  • Insulin resistance
  • Tau hyperphosphorylation

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