Scientists discover how obesity may fuel Alzheimer’s disease

The study, led by Houston Methodist researchers, examined how changes in body fat associated with obesity may send damaging signals to the brain. These signals appear to interfere with the brain's immune system and contribute to the biological damage linked to Alzheimer's disease.

The research was co-led by Stephen Wong, Ph.D., the John S. Dunn Presidential Distinguished Chair in Biomedical Engineering, and Li Yang, Ph.D., a research associate in the Chao Center for BRAIN at Houston Methodist. The findings were published in Molecular Neurodegeneration.

Fat Molecules May Connect Obesity and Alzheimer's

The researchers identified phosphatidylethanolamines (PEs) as a potentially important link between obesity and Alzheimer's disease. PEs are a class of lipid, or fat molecule, found in cell membranes throughout the body.

According to the study, obesity raises the amount of these molecules in body tissue. The PEs are then loaded into tiny particles that can travel through the body and reach the brain.

Once inside the brain, these particles can interfere with communication between brain cells, weaken immune protection, and encourage amyloid proteins to accumulate. Amyloid buildup is one of the major biological features associated with Alzheimer's disease.

"Obesity can change how signals travel to the brain," Wong said. "The good news is that this may be something we can treat. Instead of looking at Alzheimer's risk tied to obesity as just a metabolic problem, this research suggests we may be able to target the process that connects those changes to the brain."

Restoring Lipid Balance Improved Brain Function

The findings also suggest a possible direction for future treatments. When the researchers restored a healthier balance of PEs, they observed less disruption in lipid regulation.

Correcting the imbalance also improved brain function and cognitive performance in models of Alzheimer's disease. Cognitive performance refers to abilities such as learning, memory, attention, and problem solving.

These results suggest that targeting the fat molecules or the pathway that carries them to the brain could potentially reduce some of the damage associated with obesity and Alzheimer's.

A Growing Public Health Challenge

According to the Centers for Disease Control and Prevention, more than 6.5 million Americans are living with Alzheimer's. That total is expected to rise to nearly 14 million by 2060.

Yang emphasized that more research will be required before treatments aimed at PEs can be tested as prevention or therapy in people. Still, the findings introduce a possible strategy for intervening earlier in individuals whose metabolic health may place them at greater risk of Alzheimer's disease.

Study Collaborators and Funding

Other collaborators on the study include Li Yang, Jianting Sheng, Shaohua Qi, Zheng Yin, Michael Chan, Yuliang Cao, Hong Zhao, Zhihao Wan, Bill Chan, Ju Ahn, Xiaohui Yu, Matthew Vasquez and Shan Xu from Houston Methodist; Xianlin Han from the University of Texas, San Antonio; Weiming Xia from Boston University and Willa Hsueh from Ohio State University.

The study was funded by grants from the Cure Alzheimer's Fund, the T.T. and W.F. Chao Foundation, and the John S. Dunn Research Foundation.