The effect of altered nitric oxide bioavailability on the interaction of obesity and Alzheimer’s disease. Exploration of whether a high fat diet produces early cognitive decline in an Alzheimer’s mouse model.

Alzheimer’s disease (AD) can be predicted by obesity and vascular risk factors. Obesity and AD are associated with vascular dysfunction, resulting in reduced peripheral and cerebral blood flow. Obesity is associated with reduced nitric oxide (NO) bioavailability, which contributes to reduced blood flow, the accumulation of β‐amyloid (Aβ), and eventual cognitive decline in AD. In animal models of AD, obesity or high fat diet exacerbates cognitive decline. The APPswe/PS1dE9 (APP/PS1) mouse, a model of beta amyloid neuropathology, demonstrates significant NO substrate dysfunction. NO substrate dysfunction and obesity potentially initiates metabolic and vascular dysfunction that can accelerate cognitive function decline. We investigated the impact of a high‐fat diet (HFD) on cognitive performance (discrimination reversal) in transgenic (Tg) and non‐transgenic (Non‐Tg) APP/PS1 mice prior to evaluating the role of NO in AD and obesity.