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Novel Exosome Biomarker Candidates for Alzheimer’s Disease Unravelled Through Mass Spectrometry Analysis

Exosomes are small extracellular vesicles (EVs) present in human biofluids that can transport specific disease-associated molecules. Consequently blood-derived exosomes have emerged as important peripheral biomarker sources for a wide range of diseases, among them Alzheimer’s disease (AD). Although...

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Autores principales: Soares Martins, Tânia, Marçalo, Rui, da Cruz e Silva, Cristóvão B., Trindade, Dário, Catita, José, Amado, Francisco, Melo, Tânia, Rosa, Ilka Martins, Vogelgsang, Jonathan, Wiltfang, Jens, da Cruz e Silva, Odete A. B., Henriques, Ana Gabriela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016047/
https://www.ncbi.nlm.nih.gov/pubmed/35212939
http://dx.doi.org/10.1007/s12035-022-02762-1
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author Soares Martins, Tânia
Marçalo, Rui
da Cruz e Silva, Cristóvão B.
Trindade, Dário
Catita, José
Amado, Francisco
Melo, Tânia
Rosa, Ilka Martins
Vogelgsang, Jonathan
Wiltfang, Jens
da Cruz e Silva, Odete A. B.
Henriques, Ana Gabriela
author_facet Soares Martins, Tânia
Marçalo, Rui
da Cruz e Silva, Cristóvão B.
Trindade, Dário
Catita, José
Amado, Francisco
Melo, Tânia
Rosa, Ilka Martins
Vogelgsang, Jonathan
Wiltfang, Jens
da Cruz e Silva, Odete A. B.
Henriques, Ana Gabriela
author_sort Soares Martins, Tânia
collection PubMed
description Exosomes are small extracellular vesicles (EVs) present in human biofluids that can transport specific disease-associated molecules. Consequently blood-derived exosomes have emerged as important peripheral biomarker sources for a wide range of diseases, among them Alzheimer’s disease (AD). Although there is no effective cure for AD, an accurate diagnosis, relying on easily accessible peripheral biofluids, is still necessary to discriminate this disease from other dementias, test potential therapies and even monitor rate of disease progression. The ultimate goal is to produce a cost-effective and widely available alternative, which can also be employed as a first clinical screen. In this study, EVs with exosome-like characteristics were isolated from serum of Controls and AD cases through precipitation- and column-based methods, followed by mass spectrometry analysis. The resulting proteomes were characterized by Gene Ontology (GO) and multivariate analyses. Although GO terms were similar for exosomes’ proteomes of Controls and ADs, using both methodologies, a clear segregation of disease cases was obtained when using the precipitation-based method. Nine significantly different abundant proteins were identified between Controls and AD cases, representing putative biomarker candidate targets. Among them are AACT and C4BPα, two Aβ-binding proteins, whose exosome levels were further validated in individuals from independent cohorts using antibody-based approaches. The findings discussed represent an important contribution to the identification of novel exosomal biomarker candidates useful as potential blood-based tools for AD diagnosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-022-02762-1.
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spelling pubmed-90160472022-05-02 Novel Exosome Biomarker Candidates for Alzheimer’s Disease Unravelled Through Mass Spectrometry Analysis Soares Martins, Tânia Marçalo, Rui da Cruz e Silva, Cristóvão B. Trindade, Dário Catita, José Amado, Francisco Melo, Tânia Rosa, Ilka Martins Vogelgsang, Jonathan Wiltfang, Jens da Cruz e Silva, Odete A. B. Henriques, Ana Gabriela Mol Neurobiol Article Exosomes are small extracellular vesicles (EVs) present in human biofluids that can transport specific disease-associated molecules. Consequently blood-derived exosomes have emerged as important peripheral biomarker sources for a wide range of diseases, among them Alzheimer’s disease (AD). Although there is no effective cure for AD, an accurate diagnosis, relying on easily accessible peripheral biofluids, is still necessary to discriminate this disease from other dementias, test potential therapies and even monitor rate of disease progression. The ultimate goal is to produce a cost-effective and widely available alternative, which can also be employed as a first clinical screen. In this study, EVs with exosome-like characteristics were isolated from serum of Controls and AD cases through precipitation- and column-based methods, followed by mass spectrometry analysis. The resulting proteomes were characterized by Gene Ontology (GO) and multivariate analyses. Although GO terms were similar for exosomes’ proteomes of Controls and ADs, using both methodologies, a clear segregation of disease cases was obtained when using the precipitation-based method. Nine significantly different abundant proteins were identified between Controls and AD cases, representing putative biomarker candidate targets. Among them are AACT and C4BPα, two Aβ-binding proteins, whose exosome levels were further validated in individuals from independent cohorts using antibody-based approaches. The findings discussed represent an important contribution to the identification of novel exosomal biomarker candidates useful as potential blood-based tools for AD diagnosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-022-02762-1. Springer US 2022-02-25 2022 /pmc/articles/PMC9016047/ /pubmed/35212939 http://dx.doi.org/10.1007/s12035-022-02762-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Soares Martins, Tânia
Marçalo, Rui
da Cruz e Silva, Cristóvão B.
Trindade, Dário
Catita, José
Amado, Francisco
Melo, Tânia
Rosa, Ilka Martins
Vogelgsang, Jonathan
Wiltfang, Jens
da Cruz e Silva, Odete A. B.
Henriques, Ana Gabriela
Novel Exosome Biomarker Candidates for Alzheimer’s Disease Unravelled Through Mass Spectrometry Analysis
title Novel Exosome Biomarker Candidates for Alzheimer’s Disease Unravelled Through Mass Spectrometry Analysis
title_full Novel Exosome Biomarker Candidates for Alzheimer’s Disease Unravelled Through Mass Spectrometry Analysis
title_fullStr Novel Exosome Biomarker Candidates for Alzheimer’s Disease Unravelled Through Mass Spectrometry Analysis
title_full_unstemmed Novel Exosome Biomarker Candidates for Alzheimer’s Disease Unravelled Through Mass Spectrometry Analysis
title_short Novel Exosome Biomarker Candidates for Alzheimer’s Disease Unravelled Through Mass Spectrometry Analysis
title_sort novel exosome biomarker candidates for alzheimer’s disease unravelled through mass spectrometry analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016047/
https://www.ncbi.nlm.nih.gov/pubmed/35212939
http://dx.doi.org/10.1007/s12035-022-02762-1
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