High-fat diet negatively affects brain markers, cognitive behaviors, and noncognitive behaviors in the rTg4510 tau mouse model

Alzheimer's disease (AD) drastically impacts cognitive and noncognitive behaviors in both humans and animal models. Two hallmark proteins in AD, amyloid-beta plaques and tau neurofibrillary tangles, accumulate in regions of the brain critical for learning and memory, including the hippocampus. Poor dietary choices have been shown to exacerbate cognitive deficits seen in AD. In this study, we assessed the effects of a high-fat diet (HFD - 60 kcal% fat) on cognitive & noncognitive behaviors as well as on brain markers in the rTg4510 tau mouse model. While all mice learned the Morris Water Maze (MWM) task, it was noted that on the last day of acquisition female tau mice had a significantly higher latency to find the platform than male tau mice (p < 0.01). Mice given the HFD spent significantly less time in the target quadrant than those given a control diet (CD) (p < 0.05). Tau mice showed impaired burrowing (p < 0.05) and nesting behaviors (p < 0.001) compared to WT mice and HFD administration worsened burrowing in tau mice. Tau mice exhibited greater levels of glial fibrillary acidic protein (GFAP) (p < 0.05) and significantly less hippocampal cell density than WT mice (p < 0.001). We observed trends of HFD mice having greater levels of GFAP and greater average tangle size than CD mice. These results highlight the importance of dietary choices, especially in older populations more susceptible to AD and its effects.