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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-97969-y |
| _version_ | 1818344704686686208 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T16:50:43Z |
| format | Article |
| id | doaj.art-41fc1d200018460e9fa27e434581d2aa |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T16:50:43Z |
| publishDate | 2021-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-41fc1d200018460e9fa27e434581d2aa2022-12-21T23:38:03ZengNature PortfolioScientific Reports2045-23222021-09-0111111510.1038/s41598-021-97969-yShotgun-based proteomics of extracellular vesicles in Alzheimer’s disease reveals biomarkers involved in immunological and coagulation pathwaysJonas Ellegaard Nielsen0Bent Honoré1Karsten Vestergård2Raluca Georgiana Maltesen3Gunna Christiansen4Anna Uhd Bøge5Søren Risom Kristensen6Shona Pedersen7Department of Clinical Medicine, Aalborg UniversityDepartment of Clinical Medicine, Aalborg UniversityDepartment of Neurology, Aalborg University HospitalTranslational Radiation Biology and Oncology Laboratory, Centre for Cancer Research, Westmead Institute of Medical ResearchDepartment of Health Science and Technology, Aalborg UniversityDepartment of Clinical Biochemistry, Aalborg University HospitalDepartment of Clinical Medicine, Aalborg UniversityDepartment of Basic Medical Sciences, College of Medicine, Qatar UniversityAbstract 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.https://doi.org/10.1038/s41598-021-97969-y |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-97969-y |
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