Summary: A groundbreaking study reveals how obesity may drive Alzheimer’s disease through tiny messengers called extracellular vesicles released from fat tissue. These vesicles carry lipids that alter how quickly amyloid-β plaques form, a hallmark of Alzheimer’s.
Because they can cross the blood-brain barrier, they act as a direct communication line between body fat and the brain. Targeting these messengers could open new ways to prevent or slow dementia in at-risk individuals.
Key Facts:
- Fat-to-Brain Link: Extracellular vesicles from body fat can cross the blood-brain barrier.
- Plaque Formation: Vesicle lipids in obese individuals promote faster amyloid-β clumping.
- Therapeutic Potential: Blocking this signaling may reduce Alzheimer’s risk in obesity.
Source: Houston Methodist
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.
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,” said Wong, corresponding author and director of T. T. & W. F. Chao Center for BRAIN at 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 that 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.
The research was coauthored by Michael Chan, Shaohua Qi, and Bill Chan from Houston Methodist; Dharti Shantaram, Xilal Rima, Eduardo Reategui, and Willa Hsueh from The Ohio State University’s Wexner Medical Center; and Xianlin Han from the University of Texas Health Science Center at San Antonio.
About this Alzheimer’s Disease research news
Author: Amy McCaig
Source: Houston Methodist
Contact: Amy McCaig – Houston Methodist
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Decoding Adipose–Brain Crosstalk: Distinct Lipid Cargo in Human Adipose-Derived Extracellular Vesicles Modulates Amyloid Aggregation in Alzheimer’s Disease” by Stephen Wong et al. Alzheimer’s & Dementia
Abstract
Decoding Adipose–Brain Crosstalk: Distinct Lipid Cargo in Human Adipose-Derived Extracellular Vesicles Modulates Amyloid Aggregation in Alzheimer’s Disease
INTRODUCTION
Obesity is a major modifiable risk factor for Alzheimer’s disease (AD), but the mechanistic link between peripheral metabolic dysfunction and AD progression remains unclear. Adipose-derived extracellular vesicles (EVs) may penetrate the brain and alter lipid homeostasis, contributing to neurodegeneration.
METHODS
We isolated exosome-enriched EVs from subcutaneous and visceral fat of lean and obese individuals, followed by lipidomic profiling. An in vitro amyloid-β (Aβ) aggregation assay using purified Aβ40 and Aβ42 peptides was performed under lipid environments mimicking physiological and pathological states.
RESULTS
Obese-derived EVs exhibited distinct lipid profiles, particularly in lysophosphatidylcholine (LPC) and sphingomyelin (SM) species. Functional assays demonstrated that lipid identity and concentration critically influenced Aβ aggregation kinetics.
DISCUSSION
Our study reveals that obesity-associated EV lipids modulate Aβ aggregation, linking adipose metabolism to AD pathology. These findings support lipid-targeted strategies as potential therapeutics for neurodegenerative diseases.
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