Fat may secretly fuel Alzheimer’s, new research finds

A groundbreaking study from Houston Methodist has revealed that microscopic messengers released by fat tissue, known as adipose-derived extracellular vesicles, may signal the brain to form harmful amyloid-β plaques in people with obesity. These plaques are one of the defining hallmarks of Alzheimer's disease.

Tiny Cell Messengers Link Fat and Brain Health

The findings were published on October 2 in Alzheimer's & Dementia: The Journal of the Alzheimer's Association under the title "Decoding Adipose-Brain Crosstalk: Distinct Lipid Cargo in Human Adipose-Derived Extracellular Vesicles Modulates Amyloid Aggregation in Alzheimer's Disease." The study explores how obesity, which affects about 40% of Americans, may contribute to the neurodegenerative disorder that currently impacts more than 7 million people in the U.S.

The research team was led by Stephen Wong, Ph.D., the John S. Dunn Presidential Distinguished Chair in Biomedical Engineering. Collaborating with Wong were Li Yang, Ph.D., a research associate, and Jianting Sheng, Ph.D., an assistant research professor of computational biology and mathematics in radiology at the Houston Methodist Academic Institute. Together, they coordinated the study's experimental design and multi-institutional efforts.

Obesity Identified as a Leading Dementia Risk

"As recent studies have underscored, obesity is now recognized as the top modifiable risk factor for dementia in the United States," said Wong, corresponding author and director of T. T. & W. F. Chao Center for BRAIN at Houston Methodist.

The researchers discovered that these vesicles carry different lipid molecules in people with obesity compared to lean individuals. Those differences appear to influence how quickly amyloid-β proteins clump together in the brain. Using both mouse models and samples of human body fat, the scientists examined how these membrane-bound particles move through the body and affect brain processes. Remarkably, these tiny messengers can even cross the blood-brain barrier, enabling direct communication between fat tissue and the brain.

Potential Pathways for Prevention and Treatment

The team believes that targeting these vesicles and interrupting the signals that promote plaque buildup could eventually help lower Alzheimer's risk among people with obesity. Future studies, they suggest, should examine how specific drug therapies might slow or stop the accumulation of toxic Alzheimer's-related proteins (such as amyloid-β) in those at elevated risk.

In addition to the Houston Methodist team, the study's coauthors include Michael Chan, Shaohua Qi, and Bill Chan (Houston Methodist); Dharti Shantaram, Xilal Rima, Eduardo Reategui, and Willa Hsueh (The Ohio State University Wexner Medical Center); and Xianlin Han (University of Texas Health Science Center at San Antonio).