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In this study, we applied quantitative mass spectrometry-based proteomics and phosphoproteomics to characterize synaptosomes and sarkosyl-insoluble protein inclusions from the post-mortem frontal lobes of AD and control cases. We identified &amp;gt;3700 proteins across both fractions, revealing AD-associated changes in synaptic composition and phosphorylation patterns. Proteomic analyses indicated mitochondrial deficits and disruptions in vesicle trafficking within synapses, whereas insoluble protein inclusions showed an accumulation of spliceosomal components and glial activation markers as well as an enrichment of N-terminally truncated amyloid beta peptides in AD cases, suggesting involvement of postfibrillar processing events mediated by specific proteases in amyloid plaque pathology. Phosphoproteomic analysis revealed extensive alterations in pathways regulating vesicle trafficking, Golgi homeostasis, and synaptic function. We observed increased tau phosphorylation at AD-associated sites in insoluble inclusions and distinct phosphorylation changes in synaptic tau, particularly at S285 and S305, suggesting altered tau function and aggregation properties. These findings provide new molecular insights into AD-related nerve terminal composition and protein aggregation, advancing our understanding of disease-associated changes at the subcellular level.<\/jats:p>","DOI":"10.1021\/acs.jproteome.5c01160","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:59:00Z","timestamp":1783450740000},"page":"3861-3878","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic\nand Phosphoproteomic Characterization of\nDisease-Associated Alterations in Nerve Terminals and Protein Inclusions\nof Alzheimer\u2019s Disease Patients"],"prefix":"10.1021","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-1073","authenticated-orcid":true,"given":"Sofie B.","family":"Elmkvist","sequence":"first","affiliation":[{"name":"University of Southern Denmark , , ,","place":["Odense, Denmark, 5230"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla K.","family":"Thygesen","sequence":"additional","affiliation":[{"name":"University of Southern Denmark , , ,","place":["Odense, Denmark, 5230"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Jensen","sequence":"additional","affiliation":[{"name":"University of Southern Denmark , , ,","place":["Odense, Denmark, 5230"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Pihl","sequence":"additional","affiliation":[{"name":"University of Copenhagen , , ,","place":["Copenhagen, Denmark, 2200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine K.","family":"Freude","sequence":"additional","affiliation":[{"name":"University of Copenhagen , , ,","place":["Copenhagen, Denmark, 2200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bente","family":"Finsen","sequence":"additional","affiliation":[{"name":"University of Southern Denmark , , ,","place":["Odense, Denmark, 5230"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6203-0123","authenticated-orcid":true,"given":"Martin R.","family":"Larsen","sequence":"additional","affiliation":[{"name":"University of Southern Denmark , , ,","place":["Odense, Denmark, 5230"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"2026080709083286900_cit1","doi-asserted-by":"publisher","first-page":"15056","DOI":"10.1038\/nrdp.2015.56","article-title":"Alzheimer\u2019s disease","volume":"1","author":"Masters","year":"2015","journal-title":"Nat.\nRev. 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