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Adipose\u2010derived extracellular vesicles (EVs) may penetrate the brain and alter lipid homeostasis, contributing to neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We isolated exosome\u2010enriched EVs from subcutaneous and visceral fat of lean and obese individuals, followed by lipidomic profiling. An in vitro amyloid\u2010\u03b2 (A\u03b2) aggregation assay using purified A\u03b240 and A\u03b242 peptides was performed under lipid environments mimicking physiological and pathological states.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Obese\u2010derived EVs exhibited distinct lipid profiles, particularly in lysophosphatidylcholine (LPC) and sphingomyelin (SM) species. Functional assays demonstrated that lipid identity and concentration critically influenced A\u03b2 aggregation kinetics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our study reveals that obesity\u2010associated EV lipids modulate A\u03b2 aggregation, linking adipose metabolism to AD pathology. These findings support lipid\u2010targeted strategies as potential therapeutics for neurodegenerative diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Human adipose\u2010derived extracellular vesicles (EVs) from obese individuals exhibit distinct lipidomic profiles.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>EV lipids modulate amyloid\u2010\u03b2 (A\u03b2) 40 and A\u03b242 aggregation in a lipid\u2010type\u2010 and concentration\u2010dependent manner.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Lysophosphatidylcholine (LPC) and sphingomyelin (SM) species from obese EVs significantly deregulate A\u03b2 fibrillization in vitro.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>EV lipid cargo links peripheral metabolic state to amyloid pathology in Alzheimer's disease.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70603","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T11:00:05Z","timestamp":1759402805000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Decoding adipose\u2013brain crosstalk: Distinct lipid cargo in human adipose\u2010derived extracellular vesicles modulates amyloid aggregation in Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Li","family":"Yang","sequence":"first","affiliation":[{"name":"Systems Medicine and Bioengineering Department Houston Methodist Neal Cancer Center Houston Methodist Hospital  Houston Texas USA"},{"name":"Ting Tsung &amp; 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Wei Fong Chao Center for BRAIN Houston Methodist Academic Institute and Weill Cornell Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bill","family":"Chan","sequence":"additional","affiliation":[{"name":"Systems Medicine and Bioengineering Department Houston Methodist Neal Cancer Center Houston Methodist Hospital  Houston Texas USA"},{"name":"Ting Tsung &amp; Wei Fong Chao Center for BRAIN Houston Methodist Academic Institute and Weill Cornell Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharti","family":"Shantaram","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Center Division of Endocrinology Diabetes &amp; Metabolism Department of Internal Medicine The Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilal Y.","family":"Rima","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Center Division of Endocrinology Diabetes &amp; Metabolism Department of Internal Medicine The Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Reategui","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Center Division of Endocrinology Diabetes &amp; Metabolism Department of Internal Medicine The Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianlin","family":"Han","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies and Department of Medicine University of Texas Health Science Center at San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willa A.","family":"Hsueh","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Center Division of Endocrinology Diabetes &amp; Metabolism Department of Internal Medicine The Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen T. 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