Shotgun-based proteomics of extracellular vesicles in Alzheimer’s disease reveals biomarkers involved in immunological and coagulation pathways

Abstract Alzheimer’s disease (AD) is the most common form of dementia and without readily available clinical biomarkers. Blood-derived proteins are routinely used for diagnostics; however, comprehensive plasma profiling is challenging due to the dynamic range in protein concentrations. Extracellular...

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Autores principales:	Jonas Ellegaard Nielsen, Bent Honoré, Karsten Vestergård, Raluca Georgiana Maltesen, Gunna Christiansen, Anna Uhd Bøge, Søren Risom Kristensen, Shona Pedersen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/41fc1d200018460e9fa27e434581d2aa
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spelling	oai:doaj.org-article:41fc1d200018460e9fa27e434581d2aa2021-12-02T17:25:44ZShotgun-based proteomics of extracellular vesicles in Alzheimer’s disease reveals biomarkers involved in immunological and coagulation pathways10.1038/s41598-021-97969-y2045-2322https://doaj.org/article/41fc1d200018460e9fa27e434581d2aa2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97969-yhttps://doaj.org/toc/2045-2322Abstract Alzheimer’s disease (AD) is the most common form of dementia and without readily available clinical biomarkers. Blood-derived proteins are routinely used for diagnostics; however, comprehensive plasma profiling is challenging due to the dynamic range in protein concentrations. Extracellular vesicles (EVs) can cross the blood–brain barrier and may provide a source for AD biomarkers. We investigated plasma-derived EV proteins for AD biomarkers from 10 AD patients, 10 Mild Cognitive Impairment (MCI) patients, and 9 healthy controls (Con) using liquid chromatography-tandem mass spectrometry (LC–MS/MS). The ultracentrifuged EVs were washed and confirmed according to the MISEV2018 guidelines. Some AD patients presented with highly elevated FXIIIA1 (log2 FC: 4.6, p-value: 0.005) and FXIIIB (log2 FC: 4.9, p-value: 0.018). A panel of proteins was identified discriminating Con from AD (AUC: 0.91, CI: 0.67–1.00) with ORM2 (AUC: 1.00, CI: 1.00–1.00), RBP4 (AUC: 0.99, CI: 0.95–1.00), and HYDIN (AUC: 0.89, CI: 0.72–1.00) were found especially relevant for AD. This indicates that EVs provide an easily accessible matrix for possible AD biomarkers. Some of the MCI patients, with similar protein profiles as the AD group, progressed to AD within a 2-year timespan.Jonas Ellegaard NielsenBent HonoréKarsten VestergårdRaluca Georgiana MaltesenGunna ChristiansenAnna Uhd BøgeSøren Risom KristensenShona PedersenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jonas Ellegaard Nielsen Bent Honoré Karsten Vestergård Raluca Georgiana Maltesen Gunna Christiansen Anna Uhd Bøge Søren Risom Kristensen Shona Pedersen Shotgun-based proteomics of extracellular vesicles in Alzheimer’s disease reveals biomarkers involved in immunological and coagulation pathways
description	Abstract Alzheimer’s disease (AD) is the most common form of dementia and without readily available clinical biomarkers. Blood-derived proteins are routinely used for diagnostics; however, comprehensive plasma profiling is challenging due to the dynamic range in protein concentrations. Extracellular vesicles (EVs) can cross the blood–brain barrier and may provide a source for AD biomarkers. We investigated plasma-derived EV proteins for AD biomarkers from 10 AD patients, 10 Mild Cognitive Impairment (MCI) patients, and 9 healthy controls (Con) using liquid chromatography-tandem mass spectrometry (LC–MS/MS). The ultracentrifuged EVs were washed and confirmed according to the MISEV2018 guidelines. Some AD patients presented with highly elevated FXIIIA1 (log2 FC: 4.6, p-value: 0.005) and FXIIIB (log2 FC: 4.9, p-value: 0.018). A panel of proteins was identified discriminating Con from AD (AUC: 0.91, CI: 0.67–1.00) with ORM2 (AUC: 1.00, CI: 1.00–1.00), RBP4 (AUC: 0.99, CI: 0.95–1.00), and HYDIN (AUC: 0.89, CI: 0.72–1.00) were found especially relevant for AD. This indicates that EVs provide an easily accessible matrix for possible AD biomarkers. Some of the MCI patients, with similar protein profiles as the AD group, progressed to AD within a 2-year timespan.
format	article
author	Jonas Ellegaard Nielsen Bent Honoré Karsten Vestergård Raluca Georgiana Maltesen Gunna Christiansen Anna Uhd Bøge Søren Risom Kristensen Shona Pedersen
author_facet	Jonas Ellegaard Nielsen Bent Honoré Karsten Vestergård Raluca Georgiana Maltesen Gunna Christiansen Anna Uhd Bøge Søren Risom Kristensen Shona Pedersen
author_sort	Jonas Ellegaard Nielsen
title	Shotgun-based proteomics of extracellular vesicles in Alzheimer’s disease reveals biomarkers involved in immunological and coagulation pathways
title_short	Shotgun-based proteomics of extracellular vesicles in Alzheimer’s disease reveals biomarkers involved in immunological and coagulation pathways
title_full	Shotgun-based proteomics of extracellular vesicles in Alzheimer’s disease reveals biomarkers involved in immunological and coagulation pathways
title_fullStr	Shotgun-based proteomics of extracellular vesicles in Alzheimer’s disease reveals biomarkers involved in immunological and coagulation pathways
title_full_unstemmed	Shotgun-based proteomics of extracellular vesicles in Alzheimer’s disease reveals biomarkers involved in immunological and coagulation pathways
title_sort	shotgun-based proteomics of extracellular vesicles in alzheimer’s disease reveals biomarkers involved in immunological and coagulation pathways
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/41fc1d200018460e9fa27e434581d2aa
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Shotgun-based proteomics of extracellular vesicles in Alzheimer’s disease reveals biomarkers involved in immunological and coagulation pathways

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