{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:22:13Z","timestamp":1789586533115,"version":"build-2803163510"},"reference-count":60,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013129","name":"Ministry of SMEs and Startups","doi-asserted-by":"publisher","award":["S3355514"],"award-info":[{"award-number":["S3355514"]}],"id":[{"id":"10.13039\/501100013129","id-type":"DOI","asserted-by":"publisher"}]},{"award":["S3355514"],"award-info":[{"award-number":["S3355514"]}],"id":[{"id":"https:\/\/ror.org\/022c4zk48","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyloid beta (A\u03b2) oligomers are key mediators of synaptic dysfunction and neural circuit impairment in Alzheimer\u2019s disease (AD). While plasma A\u03b2 oligomerization propensity (OA\u03b2) correlates with cerebral amyloid pathology and cognitive decline, the systemic modulators of OA\u03b2 remain poorly understood. In this study, we identified the albumin interactome (albumin and its associated proteins) as a critical regulator of OA\u03b2. Selective depletion of the albumin interactome from plasma eliminated the OA\u03b2 difference between amyloid PET (A-PET)- and A-PET+ individuals. Proteomic analysis revealed widespread network alterations within the albumin interactome of A-PET+ individuals. Notably, vitronectin (VTN) was identified as a key hub protein that was significantly reduced in A-PET+ individuals. Functional assays and in silico modeling demonstrated that VTN directly bound to A\u03b2 and inhibited its oligomerization. Additionally, plasma VTN levels distinguished A-PET status. These findings suggest that systemic changes in the albumin interactome, particularly the reduction in VTN, are associated with dysregulated A\u03b2 dynamics in plasma. Our results provide novel insights into systemic mechanisms underlying AD pathology and identify VTN as a potential peripheral modulator and biomarker of cerebral amyloid pathology.<\/jats:p>","DOI":"10.3390\/ijms27135744","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:49:23Z","timestamp":1782434963000},"page":"5744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Vitronectin Modulates Plasma A\u03b2 Oligomerization Propensity Within Altered Albumin Interactome Networks in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Hojin","family":"Kang","sequence":"first","affiliation":[{"name":"PeopleBio Inc., 6th Floor, PDC C-dong, 242 Pangyo-ro, Bundang-gu, Seongnam-si 13487, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongju","family":"Kim","sequence":"additional","affiliation":[{"name":"PeopleBio Inc., 6th Floor, PDC C-dong, 242 Pangyo-ro, Bundang-gu, Seongnam-si 13487, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yonsei University College of Medicine, Yongin Severance Hospital, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si 16995, Republic of Korea"},{"name":"Institute of Behavioral Sciences in Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"},{"name":"Yonsei Graduate Program in Cognitive Science, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9409-4583","authenticated-orcid":false,"given":"Leon","family":"French","sequence":"additional","affiliation":[{"name":"Physiology Department and Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College St, Toronto, ON M5S 3E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2218-1896","authenticated-orcid":false,"given":"Hyunjung","family":"Oh","sequence":"additional","affiliation":[{"name":"PeopleBio Inc., 6th Floor, PDC C-dong, 242 Pangyo-ro, Bundang-gu, Seongnam-si 13487, Republic of Korea"},{"name":"Bionano Application Research Center, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 13120, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8123-6183","authenticated-orcid":false,"given":"Seong Soo A.","family":"An","sequence":"additional","affiliation":[{"name":"Bionano Application Research Center, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 13120, Republic of Korea"},{"name":"Department of Bionano Technology, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 13120, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","first-page":"457","article-title":"Synapse loss in frontal cortex biopsies in Alzheimer\u2019s disease: Correlation with cognitive severity","volume":"27","author":"DeKosky","year":"1990","journal-title":"Ann. 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