title: Whole-food diet worsened cognitive dysfunction in an Alzheimer's disease mouse model.
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.
authors.affiliation: Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada; Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Parrott
authors.affiliation: Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada; Department of Psychology, Trent University, Peterborough, Ontario, Canada; Department of Psychology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Winocur
authors.affiliation: Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Bazinet
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: David W L
authors.initials: DW
authors.lastname: Ma
authors.affiliation: Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada; Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada. Electronic address: carol.greenwood@utoronto.ca.
authors.forename: Carol E
authors.initials: CE
authors.lastname: Greenwood
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D003071:Cognition; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D018450:Disease Progression; D006624:Hippocampus / Q000378:metabolism; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020078:Neurogenic Inflammation / Q000209:etiology; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D014409:Tumor Necrosis Factor-alpha
keywords: Alzheimer; Cognitive function; Diet; Diet quality; Food; Mouse model; Neuroinflammation