Decoding adipose-brain crosstalk: Distinct lipid cargo in human adipose-derived extracellular vesicles modulates amyloid aggregation in Alzheimer's disease

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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. Highlights Human adipose-derived extracellular vesicles (EVs) from obese individuals exhibit distinct lipidomic profiles. EV lipids modulate amyloid-β (Aβ) 40 and Aβ42 aggregation in a lipid-type- and concentration-dependent manner. Lysophosphatidylcholine (LPC) and sphingom

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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