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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Vitronectin Modulates Plasma Aβ Oligomerization Propensity Within Altered Albumin Interactome Networks in Alzheimer’s Disease

by
Hojin Kang
1,†,
Hongju Kim
1,†,
Woo Jung Kim
2,3,4,
Leon French
5,
Hyunjung Oh
1,6,* and
Seong Soo A. An
6,7,*
1
PeopleBio Inc., 6th Floor, PDC C-dong, 242 Pangyo-ro, Bundang-gu, Seongnam-si 13487, Republic of Korea
2
Department of Psychiatry, Yonsei University College of Medicine, Yongin Severance Hospital, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si 16995, Republic of Korea
3
Institute of Behavioral Sciences in Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
4
Yonsei Graduate Program in Cognitive Science, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
5
Physiology Department and Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College St, Toronto, ON M5S 3E1, Canada
6
Bionano Application Research Center, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 13120, Republic of Korea
7
Department of Bionano Technology, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 13120, Republic of Korea
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2026, 27(13), 5744; https://doi.org/10.3390/ijms27135744 (registering DOI)
Submission received: 27 May 2026 / Revised: 17 June 2026 / Accepted: 19 June 2026 / Published: 25 June 2026
(This article belongs to the Special Issue Molecular and Systems Mechanisms of Neural Circuit Function and Plasticity)
Versions Notes

Abstract

Amyloid beta (Aβ) oligomers are key mediators of synaptic dysfunction and neural circuit impairment in Alzheimer’s disease (AD). While plasma Aβ oligomerization propensity (OAβ) correlates with cerebral amyloid pathology and cognitive decline, the systemic modulators of OAβ remain poorly understood. In this study, we identified the albumin interactome (albumin and its associated proteins) as a critical regulator of OAβ. Selective depletion of the albumin interactome from plasma eliminated the OAβ 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 Aβ 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 Aβ 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.
Keywords: Aβ oligomerization tendency; albumin interactome; vitronectin Aβ oligomerization tendency; albumin interactome; vitronectin

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MDPI and ACS Style

Kang, H.; Kim, H.; Kim, W.J.; French, L.; Oh, H.; An, S.S.A. Vitronectin Modulates Plasma Aβ Oligomerization Propensity Within Altered Albumin Interactome Networks in Alzheimer’s Disease. Int. J. Mol. Sci. 2026, 27, 5744. https://doi.org/10.3390/ijms27135744

AMA Style

Kang H, Kim H, Kim WJ, French L, Oh H, An SSA. Vitronectin Modulates Plasma Aβ Oligomerization Propensity Within Altered Albumin Interactome Networks in Alzheimer’s Disease. International Journal of Molecular Sciences. 2026; 27(13):5744. https://doi.org/10.3390/ijms27135744

Chicago/Turabian Style

Kang, Hojin, Hongju Kim, Woo Jung Kim, Leon French, Hyunjung Oh, and Seong Soo A. An. 2026. "Vitronectin Modulates Plasma Aβ Oligomerization Propensity Within Altered Albumin Interactome Networks in Alzheimer’s Disease" International Journal of Molecular Sciences 27, no. 13: 5744. https://doi.org/10.3390/ijms27135744

APA Style

Kang, H., Kim, H., Kim, W. J., French, L., Oh, H., & An, S. S. A. (2026). Vitronectin Modulates Plasma Aβ Oligomerization Propensity Within Altered Albumin Interactome Networks in Alzheimer’s Disease. International Journal of Molecular Sciences, 27(13), 5744. https://doi.org/10.3390/ijms27135744

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