Thinking fatty foods only hurt your waistline? Then you will be surprised to hear that yourbrainmight be at risk, too. A groundbreaking study from Purdue University, published in the journal Immunity, revealed that excess fat buildup inside the brain’s immune cells, called microglia, could be fuelingAlzheimer’s disease. These fat-choked microglia lose their ability to clear harmful proteins like amyloid beta, weakening the brain’s healing defenses. But here’s the hopeful twist: when scientists broke down this fat, the brain’s defense system bounced back. For decades, Alzheimer’s research focused mainly on plaques and tangles of misfolded proteins. But this new work, published in Immunity, points to fat metabolism as a hidden culprit. Microglia near amyloid plaques were found to contain twice as many fat droplets as normal cells, and cleared 40% less toxic protein. To uncover this, researchers examined brain tissue from people with Alzheimer’s disease and used advanced imaging and biochemical analyses to track how microglia processed fat when exposed to amyloid plaques. They discovered that microglia closest to plaques accumulated abnormal fat droplets, driven by an overactive enzyme called DGAT2. Further experiments in animal models showed that when DGAT2 was blocked or degraded, microglia regained their ability to clear amyloid beta, boosting neuronal health. Researchers’s team discovered that targeting this enzyme—either blocking its activity or promoting its breakdown—helped restore microglial function in Alzheimer’s models. That means the brain’s own immune system could fight disease again, something drug therapies aimed directly at plaques have failed to do. The findings suggest a radical shift in how we think about Alzheimer’s: not just “protein plaques,” but “lipid plaques” may be at the heart of brain degeneration. If future therapies can rebalance fat metabolism insidebrain cells, researchers believe it could open an entirely new path to preventing or even slowing the disease. Reference:Prakash, Priya, Manchanda, Palak, Paouri, Evi, Bisht, Kanchan, Sharma, Kaushik, Rajpoot, Jitika; Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease; Immunity; 2025; doi: 10.1016/j.immuni.2025.04.029