A Multimodality Study on the Lipid Molecular Basis of Obesity and Its Roles in Regulating Alzheimer’s Pathogenesis for Developing Potential Targeted Interventions

Scientific evidence shows the middle-aged obese population has a higher risk of developing Alzheimer’s disease (AD). The underlying reasons for this association remain elusive. This study emphasizes the connection between obesity and the development of AD. Lipid components of obesity-related fat tissue release tiny particles called exosome-enriched extracellular vesicles (EVs). These EVs mediate essential communication between fatty tissue and the brain. Our preliminary findings suggest that among the diverse lipids in these EVs, some have distinct signatures that seem to accelerate the progression of AD by promoting the buildup of harmful proteins in neuronal cells. The brain houses various neurons, microglia, and immune T-cells, playing pivotal roles in the AD landscape. We will study how certain lipids from obese fat tissue might be contributing to lipid accumulation in brain cells, potentially laying the foundation for AD onset and progression. By modeling and simulating the interactions (or crosstalk) among different brain cells, insights into their roles in AD progression can be gained. In essence, our study aims to bridge the gap in understanding between obesity, lipid-mediated communication, and the cellular dynamics in the brain that lead to AD. The outcomes of this research could offer profound insights into AD’s etiology and potential therapeutic inventions.