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

Jonas Ellegaard Nielsen; Bent Honoré; Karsten Vestergård; Raluca Georgiana Maltesen; Gunna Christiansen; Anna Uhd Bøge; Søren Risom Kristensen; Shona Pedersen

doi:10.1038/s41598-021-97969-y

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

Jonas Ellegaard Nielsen^*, Bent Honoré, Karsten Vestergård, Raluca Georgiana Maltesen, Gunna Christiansen, Anna Uhd Bøge, Søren Risom Kristensen, Shona Pedersen^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

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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.

Original language	English
Article number	18518
Journal	Scientific Reports
Volume	11
Issue number	1
Number of pages	15
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-021-97969-y
Publication status	Published - 16 Sept 2021

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title = "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 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.",

author = "Nielsen, {Jonas Ellegaard} and Bent Honor{\'e} and Karsten Vesterg{\aa}rd and Maltesen, {Raluca Georgiana} and Gunna Christiansen and B{\o}ge, {Anna Uhd} and Kristensen, {S{\o}ren Risom} and Shona Pedersen",

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AU - Nielsen, Jonas Ellegaard

AU - Honoré, Bent

AU - Vestergård, Karsten

AU - Maltesen, Raluca Georgiana

AU - Christiansen, Gunna

AU - Bøge, Anna Uhd

AU - Kristensen, Søren Risom

AU - Pedersen, Shona

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N2 - 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.

AB - 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.

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DO - 10.1038/s41598-021-97969-y

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JO - Scientific Reports

JF - Scientific Reports

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ER -

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

Abstract

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Proteomics- and Metabolomics-Based Molecular Signatures of Alzheimer's Disease - From Blood to Extracellular Vesicles

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