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Patient\u2010derived brain organoids and their extracellular vesicles (EVs) provide physiologically relevant models to study disease mechanisms and individualized drug responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We generated the largest brain organoid cohort to date, derived from 30 independent induced pluripotent stem cell (iPSC) lines from AD and control individuals. Comparative proteomic profiling was performed on both organoids and their secreted EVs to capture molecular diversity and treatment effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Organoids and EVs consistently recapitulated neuronal proteomic signatures and revealed early alterations in AD\u2010related pathways, including synaptic and neurotransmitter dysfunction. Distinct proteomic responses mirrored individual variability in selective serotonin reuptake inhibitor sensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Integrating organoid and EV data provides a systems\u2010level view of AD pathophysiology and treatment response, positioning this dual\u2010platform model as a cost\u2010effective tool for precision medicine and drug discovery.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71273","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T11:00:11Z","timestamp":1775646011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Proteomic profiling of brain organoids and extracellular vesicles identifies early Alzheimer's disease biomarkers and drug response heterogeneity"],"prefix":"10.1002","volume":"22","author":[{"given":"Rachel J.","family":"Boyd","sequence":"first","affiliation":[{"name":"Department of Genetic Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"The Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Division of Geriatric Medicine and Gerontology, Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiyun","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"The Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Sagar","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"The Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Iliuk","sequence":"additional","affiliation":[{"name":"Tymora Analytical Operations  West Lafayette Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waqar","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"The Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease Johns Hopkins University School of Medicine  Baltimore Maryland 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