Alzheimer’s disease, the most common form of dementia, affects more than 50 million individuals worldwide, with numbers projected to reach over 150 million by 2050. This debilitating condition, characterized by memory loss, cognitive impairment, and behavioral changes, has long been associated with lipids, a class of molecules that includes fats, oils, and hormones. However, the intricate relationship between Alzheimer’s and lipid metabolism has remained elusive.
Scientists at the University of California San Diego have recently shed new light on this enigma using advanced imaging technologies. In a study published in Cell Metabolism, they unveiled how lipid metabolism is altered in Alzheimer’s disease and proposed a novel strategy to target this metabolic system with existing and new drugs.
Senior and co-corresponding author Xu Chen, Ph.D., an assistant professor in the Department of Neurosciences at UC San Diego School of Medicine, explained, “Lipids have been linked to Alzheimer’s since its discovery in 1907, but the research community has primarily focused on proteins like tau. Our collaboration aimed to explore the role of lipid droplets in Alzheimer’s using state-of-the-art imaging techniques.”
Led by Yajuan Li, M.D., Ph.D., a postdoctoral researcher in the Shu Chien-Gene Lay Department of Bioengineering at UC San Diego Jacobs School of Engineering, the team employed a cutting-edge SRS (Stimulated Raman Scattering) imaging approach to examine lipid droplets in the brains of tauopathy mice. SRS imaging allows for the analysis of molecular interactions with laser light without the use of chemical dyes, which can alter the delicate lipids and compromise results.
In Alzheimer’s or similar diseases, lipid droplet metabolism can malfunction, leading to a complex interplay between neurons and immune cells in the brain. The researchers discovered that neurons in tauopathy brains accumulate excess lipids due to stress or damage, which are then offloaded to microglia, triggering an inflammatory response. This cycle of lipid accumulation and inflammation worsens over time.
Co-corresponding author Lingyan Shi, Ph.D., assistant professor of bioengineering at the Jacobs School of Engineering, explained, “Our approach uses heavy water as a metabolic probe instead of traditional chemical dyes. This provides a clearer picture of lipid metabolism and allows us to observe the dynamic changes in the brain with minimal interference.”
The team identified a critical enzyme, adenosine monophosphate-activated protein kinase (AMPK), that orchestrates this cycle. By targeting AMPK, they believe they can interrupt the cycle and potentially develop new treatments for Alzheimer’s disease. Chen is particularly enthusiastic about the possibility of repurposing existing drugs that modify lipid metabolism for this purpose.
Chen concluded, “Our findings suggest that lipid metabolism plays a crucial role in Alzheimer’s disease. We’re optimistic about the potential of repurposing existing drugs to target this system and change its course.”
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1. Source: Coherent Market Insights, Public sources, Desk research
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