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A peripheral proteomic signature of Alzheimer's disease is identified in the plasma extracellular vesicles of mild cognitive impairment patients from a memory clinic : the BIOPEXAL study
Capdevila-Bayo, Maria (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Rossi, Rosanna (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
De Rojas, Itziar (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Puerta, Raquel (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Guzman, Laura (Universitat de Barcelona. Departament de Farmacologia, Toxicologia i Química Terapèutica)
Carrasco Exposito, Marina (Universitat de Barcelona. Departament de Farmacologia, Toxicologia i Química Terapèutica)
Muñoz-Morales, Álvaro (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Olivé Roig, Clàudia (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Montrreal Navarro, Laura (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
García-González, Pablo (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Bayón-Buján, Paula (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Miguel-Romero, Andrea (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Calm, Berta (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Sotolongo Grau, Oscar (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Orellana del Río, Adelina (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Tatinya, Natalia (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Martínez, Marta (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Alegret, Montserrat (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Sanz Cartagena, Mª Pilar (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Fernández, Mª Victoria (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Marquié, Marta (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Valero, Sergi (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Montalban, Xavier (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Camins, Antoni (Universitat de Barcelona. Departament de Farmacologia, Toxicologia i Química Terapèutica)
Ramírez-Reveco, Alfredo (University Hospital Cologne. Department of Psychiatry and Psychotherapy)
Martí, Mercè (Universitat Autònoma de Barcelona. Departament de Química)
Pividori, María Isabel (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Boada, Mercè (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Ruiz Laza, Agustín (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)
Ettcheto, Miren (Universitat de Barcelona. Departament de Farmacologia, Toxicologia i Química Terapèutica)
Cano, Amanda (Ace Alzheimer Center Barcelona. Centre de Recerca i Clínica de la Memòria)

Date: 2025
Abstract: Aims: Alzheimer's disease (AD) is commonly diagnosed when neuronal damage is already established and irreversible. Achieving an accurate differential diagnosis in the preclinical and mild cognitive impairment (MCI) stage is one of the greatest challenges nowadays. Nanotechnological analysis of plasma extracellular vesicles (pEVs) are gaining attention as a promising tool for the early detection of AD pathology. This study aims to evaluate the proteomic profile of pEVs from patients with MCI and AD dementia to explore their potential as AD screening tools. Methods: pEVs were isolated by ultracentrifugation from 144 patients with MCI A-T-, MCI A+T+, and AD dementia. Nanoparticle tracking analysis and cryo-TEM were used to characterize the pEVs. CSF, serum and pEVs proteomics were carried out by using the multiplex PEA technology of Olink® proteomics, Inflammation and Neurology Explore 384 panels (768 proteins). Results: Characterization results showed that isolated plasma fraction corresponded in shape, size and concentration to EVs. Many pEVs neurology proteins involved in AD pathology significantly correlated (r > ± 0. 30, p < 0. 05) with their CSF homonyms, but not with their serum's. pEVs' proteome correlated with common AD signatures (CSF Aβ42 and pTau181, plasma pTau181, MMSE, NBACE, and Qalb) showing similar patterns to those observed with CSF biomarkers. Several pEVs neurology proteins didn't exhibit differences between the MCI A+T+ and AD dementia groups, whilst they did with MCI A-T-. Proteins in pEVs showed strong correlations with several measures of brain atrophy in MRI. Several neurology pEV proteins predicted conversion from MCI to AD dementia. Moreover, some of these showed a significant diagnostic accuracy of AD pathology. Conclusion: Preliminary results suggest that EVs biomarker signature could reflect AD pathology in the prodromal stages of AD continuum. However, further experiments are still needed for a better understanding of EVs' role in AD development and pathology dissemination.
Grants: Instituto de Salud Carlos III FI24/00029
Generalitat de Catalunya UB-LE-9115
Instituto de Salud Carlos III CD22/00125
Agencia Estatal de Investigación PID2021-122473OA-I00
Agencia Estatal de Investigación PID2022-136453OB-I00
Agencia Estatal de Investigación PDC2022-133363-I00
Ministerio de Ciencia e Innovación CPP2024-011381
Instituto de Salud Carlos III PI22/01403
Instituto de Salud Carlos III PI22/00258
Instituto de Salud Carlos III CB18/05/00010
Instituto de Salud Carlos III CB06/05/2004
Note: Altres ajuts: Barcelona City Council, subvencions per a Projectes de recerca jove i emergent 2024 grant 24S05876-001; The support from PREADAPT project, Joint Program for Neurodegenerative Diseases (JPND) grant Nº AC19/00097, and from HARPONE project, Agency for Innovation and Entrepreneurship (VLAIO) grant Nº PR067/21.
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: Prepublicació ; recerca ; Versió de l'autor
Subject: Plasma extracellular vesicles ; Alzheimer's disease ; Mild cognitive impairment proteomics ; Biomarkers

DOI: 10.21203/rs.3.rs-7847549/v1
PMID: 41282153


24 p, 3.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Research literature > Preprints

 Record created 2026-05-15, last modified 2026-05-19



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