Cell messengers signal amyloid plaque buildup in obese individuals

Obesity has long been acknowledged as a risk factor for a wide range of diseases, but a more precise link between obesity and Alzheimer's disease has remained a mystery – until now.

A first-of-its-kind study from Houston Methodist found that adipose-derived extracellular vesicles, tiny cell-to-cell messengers in the body, can signal the buildup of amyloid-β plaque in obese individuals. These plaques are a key feature of Alzheimer's disease.

The study, "Decoding Adipose–Brain Crosstalk: Distinct Lipid Cargo in Human Adipose-Derived Extracellular Vesicles Modulates Amyloid Aggregation in Alzheimer's Disease," published today in Alzheimer's & Dementia: The Journal of the Alzheimer's Association. It explores the link between obesity, which affects about 40% of the U.S population, and the dreaded neurodegenerative disease affecting more than 7 million people in the U.S.

The research was led by Stephen Wong, Ph.D., the John S. Dunn Presidential Distinguished Chair in Biomedical Engineering . Alongside Wong, Li Yang, Ph.D., a research associate at Houston Methodist, and Jianting Sheng, Ph.D., an assistant research professor of computational biology and mathematics in radiology at the Houston Methodist Academic Institute, provided leadership in experimental design and cross-institution coordination.

As recent studies have underscored, obesity is now recognized as the top modifiable risk factor for dementia in the United States."

Stephen Wong, Study Corresponding Author and Director, T. T. & W. F. Chao Center for BRAIN, Houston Methodist

The researchers found that the lipid cargo of these cell messengers differs between people with obesity and lean individuals, and that the presence and levels of specific lipids that differed between the groups changed how quickly amyloid-β clumped together in laboratory models. Using mouse models and patient body fat samples, the researchers examined the vesicles, which are tiny, membrane-bound particles that travel throughout the body and act as messengers involved in cell-to-cell communication. These minuscule communicators are also capable of crossing the blood-brain barrier.

Targeting these tiny cell messengers and disrupting their communication, which leads to plaque formation, may help reduce the risk of Alzheimer's disease in people with obesity. The researchers said future work should focus on how drug therapy could stop or slow the build-up of Alzheimer's-related toxic proteins (such as amyloid-β) in at-risk individuals.