Unlocking the Link Between Alzheimer's Disease and Lipid Metabolism: A New Frontier for Treatment

Saturday - April 27 2024, 23:13 UTC - 9 months ago

A study from UC San Diego has revealed the changes in lipid metabolism in Alzheimer's disease and a potential new strategy for targeting this pathway with drugs. By examining lipid droplets in the brains of mice, the researchers found a link between lipid metabolism and the disease, paving the way for further research and potential treatments.

Alzheimer's disease, the most common type of dementia, significantly impairs memory, thinking, and behavior, affecting over 50 million people globally each year. Projections suggest that this number will triple by 2050. This neurodegenerative disease, named after German psychiatrist Alois Alzheimer who first described it in 1906, is characterized by progressive cognitive decline and is the leading cause of dementia among older adults. While scientists have identified certain risk factors and genetic mutations that increase the likelihood of developing Alzheimer's disease, the exact mechanisms behind its development and progression remain largely unknown.

In a groundbreaking study, scientists at the University of California San Diego have shed light on a new aspect of Alzheimer's disease: lipid metabolism. Published in the journal Cell Metabolism, the study reveals how the metabolism of lipids, a class of molecules that includes fats, oils, and many hormones, is changed in Alzheimer's disease. By using their own state-of-the-art imaging technologies, the team also discovered a new strategy to target this metabolic system with new and existing drugs.

Lipids have long been associated with Alzheimer's disease, ever since Alois Alzheimer's original 1906 report that described the unusual presence of fat deposits in the brain of the first person to be diagnosed with the disease. Despite this early observation, the research community has largely overlooked this important aspect of the disease and instead focused on other factors like tau and other proteins.

But researchers Xu Chen, Ph.D., an assistant professor in the Department of Neurosciences at UC San Diego School of Medicine, and 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, were drawn to understanding the role of lipid droplets in aging and disease. These droplets, which come in the form of tiny globules, play important roles in processes such as energy storage and cellular responses to stress. In typical brains, these processes are tightly regulated, but in Alzheimer's disease or other neurodegenerative diseases, lipid droplet metabolism can malfunction. However, exactly how they influence one another has remained a mystery.

To address this issue, the team used a cutting-edge imaging platform developed by Lingyan Shi, Ph.D., assistant professor of bioengineering at the Jacobs School. This platform, known as stimulated Raman scattering (SRS) imaging, allows for microscopic images of lipid droplets within cells without the need for chemical dyes, which can alter the delicate molecules and compromise the results. With this technology, the team was able to directly observe the changes in lipid droplets in the brains of mice with excess tau protein.

The results were intriguing: the inert lipid droplets observed in the Alzheimer's mouse brains displayed similar behaviors to those found in aging brains. This suggests a potential link between the two processes and opens up new avenues for further research. As co-corresponding author Lingyan Shi puts it, "Our approach is biologically neutral, so we're able to observe what's happening in the brain at the molecular level without any interference from external factors. We are now focusing on understanding the underlying mechanisms by combining SRS with other multidisciplinary techniques. These findings highlight the importance of considering lipid metabolism in the study of neurodegenerative diseases, and could potentially lead to the development of new treatments or repurposing of existing drugs to target this pathway.