A diet enriched with fish, vegetables, and fruits worsened cognitive function and neuroinflammatory gene expression in a transgenic mouse model of Alzheimer's disease

Abstract

Consumption of fish, fruits and vegetables are associated with lower incidence of Alzheimer's disease (AD). We hypothesized that a similar dietary profile would improve cognitive function in a transgenic mouse model of AD. Groups of TgCRND8 mice, and their wildtype littermates, received a standard rodent diet or the standard diet enriched with freeze‐dried salmon, vegetables, and fruits over four months. During the last month of feeding, cognitive function was assessed by a comprehensive battery of tasks adapted to the Morris water maze. Transgenic animals were impaired on all cognitive tests compared to their wildtype littermates. Unexpectedly, a ‘Diet x Transgene’ interaction was observed in which transgenic animals fed the enriched diet exhibited even worse cognitive function than their transgenic counterparts fed the control diet on tests of spatial memory (P<0.01), cued memory (P<0.01), and strategic rule learning (P=0.038) that collectively indicated damage to the hippocampus and frontal lobes. These cognitive deficits coincided with higher hippocampal gene expression of tumor necrosis factor‐alpha (P=0.013). These results indicate that a dietary profile identified by epidemiological studies exacerbated cognitive dysfunction in a mouse model of familial AD possibly by enhancing neuroinflammation through an impaired hormetic response. (CIHR)