α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies

<h3>Background</h3><p dir="ltr">The objective of this study was to investigate the discriminating value of a range of CSF α‐synuclein species for dementia with Lewy bodies compared with Alzheimer's disease, PD, and cognitively normal controls.</p><p><b...

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Main Author: Inger van Steenoven (18628753) (author)
Other Authors: Nour K. Majbour (8809316) (author), Nishant N. Vaikath (2901785) (author), Henk W. Berendse (8809328) (author), Wiesje M. van der Flier (7545977) (author), Wilma D.J. van de Berg (18518109) (author), Charlotte E. Teunissen (7830647) (author), Afina W. Lemstra (8993321) (author), Omar M.A. El‐Agnaf (18628756) (author)
Published: 2018
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_version_ 1864513513545793536
author Inger van Steenoven (18628753)
author2 Nour K. Majbour (8809316)
Nishant N. Vaikath (2901785)
Henk W. Berendse (8809328)
Wiesje M. van der Flier (7545977)
Wilma D.J. van de Berg (18518109)
Charlotte E. Teunissen (7830647)
Afina W. Lemstra (8993321)
Omar M.A. El‐Agnaf (18628756)
author2_role author
author
author
author
author
author
author
author
author_facet Inger van Steenoven (18628753)
Nour K. Majbour (8809316)
Nishant N. Vaikath (2901785)
Henk W. Berendse (8809328)
Wiesje M. van der Flier (7545977)
Wilma D.J. van de Berg (18518109)
Charlotte E. Teunissen (7830647)
Afina W. Lemstra (8993321)
Omar M.A. El‐Agnaf (18628756)
author_role author
dc.creator.none.fl_str_mv Inger van Steenoven (18628753)
Nour K. Majbour (8809316)
Nishant N. Vaikath (2901785)
Henk W. Berendse (8809328)
Wiesje M. van der Flier (7545977)
Wilma D.J. van de Berg (18518109)
Charlotte E. Teunissen (7830647)
Afina W. Lemstra (8993321)
Omar M.A. El‐Agnaf (18628756)
dc.date.none.fl_str_mv 2018-11-15T03:00:00Z
dc.identifier.none.fl_str_mv 10.1002/mds.111
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/_Synuclein_species_as_potential_cerebrospinal_fluid_biomarkers_for_dementia_with_lewy_bodies/25919452
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Neurosciences
biomarkers
CSF
α-synuclein
dementia with Lewy bodies
dc.title.none.fl_str_mv α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <h3>Background</h3><p dir="ltr">The objective of this study was to investigate the discriminating value of a range of CSF α‐synuclein species for dementia with Lewy bodies compared with Alzheimer's disease, PD, and cognitively normal controls.</p><p><br></p><h3>Methods</h3><p dir="ltr">We applied our recently published enzyme‐linked immunosorbent assays to measure the CSF levels of total α‐synuclein, oligomeric α‐synuclein, and phosphorylated α‐synuclein in dementia with Lewy bodies (n = 42), Alzheimer's disease (n = 39), PD (n = 46), and controls (n = 78). General linear models corrected for age and sex were performed to assess differences in α‐synuclein levels between groups. We used backward‐elimination logistic regression analysis to investigate the combined discriminating value of the different CSF α‐synuclein species and Alzheimer's disease biomarkers.</p><p><br></p><h3>Results</h3><p dir="ltr">CSF levels of total α‐synuclein were lower in dementia with Lewy bodies and PD compared with Alzheimer's disease as well as controls (P < 0.001). In contrast, CSF levels of oligomeric α‐synuclein were higher in dementia with Lewy bodies and PD compared with Alzheimer's disease (P < 0.05) and controls (P < 0.001). No group differences were found for phosphorylated α‐synuclein. In dementia with Lewy bodies and PD, CSF total α‐synuclein levels positively correlated with tau and phosphorylated tau (both r > 0.40, P < 0.01), but not with amyloid‐β1‐42. The optimal combination to differentiate dementia with Lewy bodies from controls consisted of amyloid‐β1‐42, tau, total α‐synuclein, oligomeric α‐synuclein, age, and sex (AUC, 0.90). To differentiate dementia with Lewy bodies from Alzheimer's disease, the combination of tau and oligomeric α‐synuclein resulted in an AUC of 0.83. CSF α‐synuclein species do not contribute to the differentiation of dementia with Lewy bodies from PD.</p><p><br></p><h3>Conclusions</h3><p dir="ltr">CSF α‐synuclein species could be useful as part of a biomarker panel for dementia with Lewy bodies. Evaluating both oligomeric α‐synuclein and total α‐synuclein in CSF helps in the diagnosis of dementia with Lewy bodies. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.</p><p dir="ltr"><br></p><h2>Other Information</h2><p dir="ltr">Published in: Movement Disorders<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1002/mds.111" target="_blank">https://dx.doi.org/10.1002/mds.111</a></p>
eu_rights_str_mv openAccess
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identifier_str_mv 10.1002/mds.111
network_acronym_str Manara2
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oai_identifier_str oai:figshare.com:article/25919452
publishDate 2018
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rights_invalid_str_mv CC BY 4.0
spelling α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodiesInger van Steenoven (18628753)Nour K. Majbour (8809316)Nishant N. Vaikath (2901785)Henk W. Berendse (8809328)Wiesje M. van der Flier (7545977)Wilma D.J. van de Berg (18518109)Charlotte E. Teunissen (7830647)Afina W. Lemstra (8993321)Omar M.A. El‐Agnaf (18628756)Biomedical and clinical sciencesNeurosciencesbiomarkersCSFα-synucleindementia with Lewy bodies<h3>Background</h3><p dir="ltr">The objective of this study was to investigate the discriminating value of a range of CSF α‐synuclein species for dementia with Lewy bodies compared with Alzheimer's disease, PD, and cognitively normal controls.</p><p><br></p><h3>Methods</h3><p dir="ltr">We applied our recently published enzyme‐linked immunosorbent assays to measure the CSF levels of total α‐synuclein, oligomeric α‐synuclein, and phosphorylated α‐synuclein in dementia with Lewy bodies (n = 42), Alzheimer's disease (n = 39), PD (n = 46), and controls (n = 78). General linear models corrected for age and sex were performed to assess differences in α‐synuclein levels between groups. We used backward‐elimination logistic regression analysis to investigate the combined discriminating value of the different CSF α‐synuclein species and Alzheimer's disease biomarkers.</p><p><br></p><h3>Results</h3><p dir="ltr">CSF levels of total α‐synuclein were lower in dementia with Lewy bodies and PD compared with Alzheimer's disease as well as controls (P < 0.001). In contrast, CSF levels of oligomeric α‐synuclein were higher in dementia with Lewy bodies and PD compared with Alzheimer's disease (P < 0.05) and controls (P < 0.001). No group differences were found for phosphorylated α‐synuclein. In dementia with Lewy bodies and PD, CSF total α‐synuclein levels positively correlated with tau and phosphorylated tau (both r > 0.40, P < 0.01), but not with amyloid‐β1‐42. The optimal combination to differentiate dementia with Lewy bodies from controls consisted of amyloid‐β1‐42, tau, total α‐synuclein, oligomeric α‐synuclein, age, and sex (AUC, 0.90). To differentiate dementia with Lewy bodies from Alzheimer's disease, the combination of tau and oligomeric α‐synuclein resulted in an AUC of 0.83. CSF α‐synuclein species do not contribute to the differentiation of dementia with Lewy bodies from PD.</p><p><br></p><h3>Conclusions</h3><p dir="ltr">CSF α‐synuclein species could be useful as part of a biomarker panel for dementia with Lewy bodies. Evaluating both oligomeric α‐synuclein and total α‐synuclein in CSF helps in the diagnosis of dementia with Lewy bodies. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.</p><p dir="ltr"><br></p><h2>Other Information</h2><p dir="ltr">Published in: Movement Disorders<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1002/mds.111" target="_blank">https://dx.doi.org/10.1002/mds.111</a></p>2018-11-15T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1002/mds.111https://figshare.com/articles/journal_contribution/_Synuclein_species_as_potential_cerebrospinal_fluid_biomarkers_for_dementia_with_lewy_bodies/25919452CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259194522018-11-15T03:00:00Z
spellingShingle α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies
Inger van Steenoven (18628753)
Biomedical and clinical sciences
Neurosciences
biomarkers
CSF
α-synuclein
dementia with Lewy bodies
status_str publishedVersion
title α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies
title_full α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies
title_fullStr α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies
title_full_unstemmed α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies
title_short α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies
title_sort α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies
topic Biomedical and clinical sciences
Neurosciences
biomarkers
CSF
α-synuclein
dementia with Lewy bodies