Whole-food diet worsened cognitive dysfunction in an Alzheimer's disease mouse model

Neurobiol Aging. 2015 Jan;36(1):90-9. doi: 10.1016/j.neurobiolaging.2014.08.013. Epub 2014 Aug 16.

Abstract

Food combinations have been associated with lower incidence of Alzheimer's disease. We hypothesized that a combination whole-food diet containing freeze-dried fish, vegetables, and fruits would improve cognitive function in TgCRND8 mice by modulating brain insulin signaling and neuroinflammation. Cognitive function was assessed by a comprehensive battery of tasks adapted to the Morris water maze. Unexpectedly, a "Diet × Transgene" interaction was observed in which transgenic animals fed the whole-food diet exhibited even worse cognitive function than their transgenic counterparts fed the control diet on tests of spatial memory (p < 0.01) and strategic rule learning (p = 0.034). These behavioral deficits coincided with higher hippocampal gene expression of tumor necrosis factor-α (p = 0.013). There were no differences in cortical amyloid-β peptide species according to diet. These results indicate that a dietary profile identified from epidemiologic studies exacerbated cognitive dysfunction and neuroinflammation in a mouse model of familial Alzheimer's disease. We suggest that normally adaptive cellular responses to dietary phytochemicals were impaired by amyloid-beta deposition leading to increased oxidative stress, neuroinflammation, and behavioral deficits.

Keywords: Alzheimer; Cognitive function; Diet; Diet quality; Food; Mouse model; Neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / psychology*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cognition*
  • Diet / adverse effects*
  • Disease Models, Animal
  • Disease Progression
  • Hippocampus / metabolism
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurogenic Inflammation / etiology
  • Oxidative Stress
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Amyloid beta-Peptides
  • Tumor Necrosis Factor-alpha