To investigate the impact of dietary fats on Alzheimer's disease-related inflammatory changes (360G-Wellcome-202354_Z_16_Z)

Obesity is a low-grade inflammatory condition and a major risk factor for age-related cognitive decline, including dementia and Alzheimer’s disease (AD). Inflammation in the brain, regulated by microglial cells, is characteristic of these conditions and may contribute to obesity-related dysfunction. The infiltration of peripheral immune cells into the brain is also implicated in this inflammatory state. The AD-associated beta-amyloid peptide (Abeta) also accumulates in the brain and circulation of obese individuals. Abeta induces the same response as some bacteria; biasing microglia towards a pro- rather than anti-inflammatory state. Diets rich in saturated fats (SFA) impact negatively on health, while the benefits of unsaturated fats are well known. This extends to the brain, as polyunsaturated fats (PUFA) promote cognitive function. PUFA are of limited therapeutic use as they are not a viable dietary replacement for SFA. Monounsaturated fats (MUFA) primarily constitute the ‘Mediterranean diet’, and are contained in many health-promoting foods. MUFA can alleviate SFA-induced inflammation, but their ability to mediate the inflammatory response in the brain, or potential to promote neurological health under obesogenic conditions have not been determined. We will evaluate whether SFA primes Abeta-induced activation of glia and macrophages, and further assess whether MUFA may alleviate Abeta-induced inflammation.