biostudies-literatureYang LT. T. and W. F. Chao FoundationCure Alzheimer's FundNIA NIH HHSHouston Methodist Cornerstone AwardJohn S. Dunn Research FoundationNIH HHSPaul Richard Jeanneret Research Funde70603https://www.ebi.ac.uk/biostudies/studies/S-EPMC12489747biostudies-literatureUnknown21(10)<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Obese-derived EVs exhibited distinct lipid profiles, particularly in lysophosphatidylcholine (LPC) and sphingomyelin (SM) species. FunctionAlzheimer's & dementia : the journal of the Alzheimer's AssociationDecoding adipose-brain crosstalk: Distinct lipid cargo in human adipose-derived extracellular vesicles modulates amyloid aggregation in Alzheimer's disease.PMC12489747U01CA253553P30 AG013319R01CA238727R01AG057635P30 AG044271Sheng JYang LChan MReategui EHan XWong STCHsueh WAShantaram DQi SRima XYChan BfalseDecoding adipose-brain crosstalk: Distinct lipid cargo in human adipose-derived extracellular vesicles modulates amyloid aggregation in Alzheimer's disease.<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Obese-derived EVs exhibited distinct lipid profiles, particularly in lysophosphatidylcholine (LPC) and sphingomyelin (SM) species. Function2025-01-01T00:00:00Z2025 Oct2026-06-04T02:29:24.948Z2026-05-04T03:13:36.126ZS-EPMC124897474103670910.1002/alz.70603