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March 19, 2004The FASEB Journal

Diet‐induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer's disease

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Authors

LHLap HoChinese University of Hong KongWQWeiping QinJilin UniversityPPPatrick N. PomplMount Sinai Hospital

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Implication

Animal study demonstrates that diet-induced insulin resistance accelerates amyloid pathology in transgenic mice, suggesting defective insulin signaling drives Alzheimer's disease progression.

Key Points

  • To examine whether diet-induced insulin resistance exacerbates amyloid-beta generation, plaque accumulation, and cognitive impairment in a transgenic mouse model of Alzheimer's disease.
  • Fed Tg2576 transgenic Alzheimer's disease model mice diets designed to induce Type II diabetes-like insulin resistance versus normoglycemic controls.
  • Assessed brain beta-amyloid levels, gamma-secretase and insulin degrading enzyme activities, amyloid plaque burden, and spatial memory via the Morris water maze.
  • Measured insulin receptor signaling pathway markers, including insulin receptor autophosphorylation, PI3-kinase/AKT activation, and GSK-3 phosphorylation.
  • Diet-induced insulin resistance significantly elevated brain Abeta1-40 and Abeta1-42 levels, increased gamma-secretase activity, decreased insulin degrading enzyme activity, and worsened spatial memory performance.
  • Insulin-resistant mice exhibited reduced insulin receptor beta-subunit autophosphorylation and PI3-kinase/AKT activity, accompanied by decreased inhibitory phosphorylation of GSK-3alpha and GSK-3beta that correlated with enhanced amyloid precursor protein cleavage.

Cite This Study

Ho et al. (2004) studied this question.

synapsesocial.com/papers/6a720319fe4101aa97e0bd27https://doi.org/10.1096/fj.03-0978fje
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