The Effect Of High-Fat, Western Diet Vs. Plant-Based, Mediterranean Diet On Alzheimer's Pathology In Mice

Abstract

Every 65 seconds, someone is diagnosed with Alzheimer's Disease (AD). Individuals suffering from AD experience both behavioral and psychological symptoms, such as cognitive decline, memory deficits, and confusion. Two hallmark pathologies of AD include amyloid-beta (A-beta) and inflammation. The peptide A-beta is derived from the amyloidogenic cleavage process of amyloid precursor protein (APP). Although inflammation is a natural process induced by the innate immune response, chronic inflammation can render serious consequences that contribute to the development of AD pathologies. Simultaneously, the accumulation of A-beta and chronic inflammation can lead to neurodegeneration, neuronal death, and cognitive dysfunction. As AD prevalence rapidly increases, researchers are investigating potential therapeutic interventions that may attenuate AD pathologies and cognitive decline. Some notorious risk factors for AD include insulin resistance and obesity, and accumulating evidence also suggests that dietary factors play a pertinent role in AD development. Prior research has found that several components of the Western diet, including saturated fatty acids, refined sugar, and animal product consumption, are associated with higher AD prevalence. Conversely, plant-based diets, such as the Mediterranean diet, that contain low quantities of saturated fatty acids and high quantities of polyunsaturated fatty acids, and monounsaturated fatty acids have demonstrated therapeutic potential against AD pathologies. Therefore, the current study hypothesized that long-term consumption of a plant-based, Mediterranean diet would reduce cognitive decline induced by A-beta accumulation and inflammation in C56BL/6J mice. At two months of age, mice were assigned to one of the following diet conditions: a plant-based, Mediterranean diet, the Western diet, or a standard (control) diet for four months. Following diet consumption, mice underwent behavioral testing. Our laboratory has utilized lipopolysaccharide (LPS) in previous experiments to induce an immune challenge that increases soluble A-beta and cognitive deficits which resemble AD development. Mice were treated with LPS or sterile saline and subject to contextual fear conditioning to measure cognitive deficits induced by LPS following long-term diet consumption. We hypothesized that the plant-based, Mediterranean diet would protect mice against cognitive deficits and AD-like pathologies induced by LPS treatment, in comparison to the Western diet.