Proteomic comparison between non‐purified cerebrospinal fluid and cerebrospinal fluid‐derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia

Abstract Dementia is a leading cause of death worldwide, with increasing prevalence as global life expectancy increases. The most common neurodegenerative disorders are Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). With this study, we too...

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Main Authors: Yael Hirschberg, Natalia Valle‐Tamayo, Oriol Dols‐Icardo, Sebastiaan Engelborghs, Bart Buelens, Roosmarijn E. Vandenbroucke, Yannick Vermeiren, Kurt Boonen, Inge Mertens
Format: Article
Language:English
Published: Wiley 2023-12-01
Series:Journal of Extracellular Vesicles
Subjects:
Online Access:https://doi.org/10.1002/jev2.12383
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author Yael Hirschberg
Natalia Valle‐Tamayo
Oriol Dols‐Icardo
Sebastiaan Engelborghs
Bart Buelens
Roosmarijn E. Vandenbroucke
Yannick Vermeiren
Kurt Boonen
Inge Mertens
author_facet Yael Hirschberg
Natalia Valle‐Tamayo
Oriol Dols‐Icardo
Sebastiaan Engelborghs
Bart Buelens
Roosmarijn E. Vandenbroucke
Yannick Vermeiren
Kurt Boonen
Inge Mertens
author_sort Yael Hirschberg
collection DOAJ
description Abstract Dementia is a leading cause of death worldwide, with increasing prevalence as global life expectancy increases. The most common neurodegenerative disorders are Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). With this study, we took an in‐depth look at the proteome of the (non‐purified) cerebrospinal fluid (CSF) and the CSF‐derived extracellular vesicles (EVs) of AD, PD, PD‐MCI (Parkinson's disease with mild cognitive impairment), PDD and DLB patients analysed by label‐free mass spectrometry. This has led to the discovery of differentially expressed proteins that may be helpful for differential diagnosis. We observed a greater number of differentially expressed proteins in CSF‐derived EV samples (N = 276) compared to non‐purified CSF (N = 169), with minimal overlap between both datasets. This finding suggests that CSF‐derived EV samples may be more suitable for the discovery phase of a biomarker study, due to the removal of more abundant proteins, resulting in a narrower dynamic range. As disease‐specific markers, we selected a total of 39 biomarker candidates identified in non‐purified CSF, and 37 biomarker candidates across the different diseases under investigation in the CSF‐derived EV data. After further exploration and validation of these proteins, they can be used to further differentiate between the included dementias and may offer new avenues for research into more disease‐specific pharmacological therapeutics.
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spelling doaj.art-fd1aaeeff9694aa29093821377144e732023-12-27T09:15:41ZengWileyJournal of Extracellular Vesicles2001-30782023-12-011212n/an/a10.1002/jev2.12383Proteomic comparison between non‐purified cerebrospinal fluid and cerebrospinal fluid‐derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementiaYael Hirschberg0Natalia Valle‐Tamayo1Oriol Dols‐Icardo2Sebastiaan Engelborghs3Bart Buelens4Roosmarijn E. Vandenbroucke5Yannick Vermeiren6Kurt Boonen7Inge Mertens8Health Unit Flemish Institute for Technological Research (VITO) Mol BelgiumDepartment of Neurology, Sant Pau Memory Unit, Sant Pau Biomedical Research Institute Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Barcelona SpainDepartment of Neurology, Sant Pau Memory Unit, Sant Pau Biomedical Research Institute Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Barcelona SpainDepartment of Neurology and Bru‐BRAIN Universitair Ziekenhuis Brussel and NEUR Research Group, Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB) Brussels BelgiumData Science Hub, Flemish Institute for Technological Research (VITO) Mol BelgiumVIB Center for Inflammation Research, VIB Ghent BelgiumFaculty of Medicine & Health Sciences, Translational Neurosciences University of Antwerp Antwerp BelgiumHealth Unit Flemish Institute for Technological Research (VITO) Mol BelgiumHealth Unit Flemish Institute for Technological Research (VITO) Mol BelgiumAbstract Dementia is a leading cause of death worldwide, with increasing prevalence as global life expectancy increases. The most common neurodegenerative disorders are Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). With this study, we took an in‐depth look at the proteome of the (non‐purified) cerebrospinal fluid (CSF) and the CSF‐derived extracellular vesicles (EVs) of AD, PD, PD‐MCI (Parkinson's disease with mild cognitive impairment), PDD and DLB patients analysed by label‐free mass spectrometry. This has led to the discovery of differentially expressed proteins that may be helpful for differential diagnosis. We observed a greater number of differentially expressed proteins in CSF‐derived EV samples (N = 276) compared to non‐purified CSF (N = 169), with minimal overlap between both datasets. This finding suggests that CSF‐derived EV samples may be more suitable for the discovery phase of a biomarker study, due to the removal of more abundant proteins, resulting in a narrower dynamic range. As disease‐specific markers, we selected a total of 39 biomarker candidates identified in non‐purified CSF, and 37 biomarker candidates across the different diseases under investigation in the CSF‐derived EV data. After further exploration and validation of these proteins, they can be used to further differentiate between the included dementias and may offer new avenues for research into more disease‐specific pharmacological therapeutics.https://doi.org/10.1002/jev2.12383biomarkerscerebrospinal fluiddementiaextracellular vesiclesmass spectrometryproteomics
spellingShingle Yael Hirschberg
Natalia Valle‐Tamayo
Oriol Dols‐Icardo
Sebastiaan Engelborghs
Bart Buelens
Roosmarijn E. Vandenbroucke
Yannick Vermeiren
Kurt Boonen
Inge Mertens
Proteomic comparison between non‐purified cerebrospinal fluid and cerebrospinal fluid‐derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia
Journal of Extracellular Vesicles
biomarkers
cerebrospinal fluid
dementia
extracellular vesicles
mass spectrometry
proteomics
title Proteomic comparison between non‐purified cerebrospinal fluid and cerebrospinal fluid‐derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia
title_full Proteomic comparison between non‐purified cerebrospinal fluid and cerebrospinal fluid‐derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia
title_fullStr Proteomic comparison between non‐purified cerebrospinal fluid and cerebrospinal fluid‐derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia
title_full_unstemmed Proteomic comparison between non‐purified cerebrospinal fluid and cerebrospinal fluid‐derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia
title_short Proteomic comparison between non‐purified cerebrospinal fluid and cerebrospinal fluid‐derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia
title_sort proteomic comparison between non purified cerebrospinal fluid and cerebrospinal fluid derived extracellular vesicles from patients with alzheimer s parkinson s and lewy body dementia
topic biomarkers
cerebrospinal fluid
dementia
extracellular vesicles
mass spectrometry
proteomics
url https://doi.org/10.1002/jev2.12383
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