Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease

<h3>Background</h3><p dir="ltr">Despite decades of intensive research, to date, there is no accepted diagnosis for Parkinson’s disease (PD) based on biochemical analysis of blood or CSF. However, neurodegeneration in the brains of PD patients begins several years before t...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Nour K. Majbour (8809316) (author)
مؤلفون آخرون: Nishant N. Vaikath (2901785) (author), Karin D. van Dijk (18891685) (author), Mustafa T. Ardah (4858657) (author), Shiji Varghese (291775) (author), Louise B. Vesterager (19738231) (author), Liliana P. Montezinho (19738234) (author), Stephen Poole (607442) (author), Bared Safieh-Garabedian (3554684) (author), Takahiko Tokuda (105837) (author), Charlotte E. Teunissen (7830647) (author), Henk W. Berendse (8809328) (author), Wilma D. J. van de Berg (8809325) (author), Omar M. A. El-Agnaf (8809331) (author)
منشور في: 2016
الموضوعات:
الوسوم: إضافة وسم
لا توجد وسوم, كن أول من يضع وسما على هذه التسجيلة!
_version_ 1864513556013121536
author Nour K. Majbour (8809316)
author2 Nishant N. Vaikath (2901785)
Karin D. van Dijk (18891685)
Mustafa T. Ardah (4858657)
Shiji Varghese (291775)
Louise B. Vesterager (19738231)
Liliana P. Montezinho (19738234)
Stephen Poole (607442)
Bared Safieh-Garabedian (3554684)
Takahiko Tokuda (105837)
Charlotte E. Teunissen (7830647)
Henk W. Berendse (8809328)
Wilma D. J. van de Berg (8809325)
Omar M. A. El-Agnaf (8809331)
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author_facet Nour K. Majbour (8809316)
Nishant N. Vaikath (2901785)
Karin D. van Dijk (18891685)
Mustafa T. Ardah (4858657)
Shiji Varghese (291775)
Louise B. Vesterager (19738231)
Liliana P. Montezinho (19738234)
Stephen Poole (607442)
Bared Safieh-Garabedian (3554684)
Takahiko Tokuda (105837)
Charlotte E. Teunissen (7830647)
Henk W. Berendse (8809328)
Wilma D. J. van de Berg (8809325)
Omar M. A. El-Agnaf (8809331)
author_role author
dc.creator.none.fl_str_mv Nour K. Majbour (8809316)
Nishant N. Vaikath (2901785)
Karin D. van Dijk (18891685)
Mustafa T. Ardah (4858657)
Shiji Varghese (291775)
Louise B. Vesterager (19738231)
Liliana P. Montezinho (19738234)
Stephen Poole (607442)
Bared Safieh-Garabedian (3554684)
Takahiko Tokuda (105837)
Charlotte E. Teunissen (7830647)
Henk W. Berendse (8809328)
Wilma D. J. van de Berg (8809325)
Omar M. A. El-Agnaf (8809331)
dc.date.none.fl_str_mv 2016-01-19T03:00:00Z
dc.identifier.none.fl_str_mv 10.1186/s13024-016-0072-9
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Oligomeric_and_phosphorylated_alpha-synuclein_as_potential_CSF_biomarkers_for_Parkinson_s_disease/27101698
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
Parkinson’s disease
Alpha synuclein
Cerebrospinal fluid biomarkers
Amyloid oligomers
Biomarkers
dc.title.none.fl_str_mv Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease
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">Despite decades of intensive research, to date, there is no accepted diagnosis for Parkinson’s disease (PD) based on biochemical analysis of blood or CSF. However, neurodegeneration in the brains of PD patients begins several years before the manifestation of the clinical symptoms, pointing to serious flaw/limitations in this approach.</p><h3>Results</h3><p dir="ltr">To explore the potential use of alpha-synuclein (α-syn) species as candidate biomarkers for PD, we generated specific antibodies directed against wide array of α-syn species, namely total-, oligomeric- and phosphorylated-Ser129-α-syn (t-, o- and p-S129-α-syn). Next we sought to employ our antibodies to develop highly specific ELISA assays to quantify α-syn species in biological samples. Finally we verified the usefulness of our assays in CSF samples from 46 PD patients and 48 age-matched healthy controls. We also assessed the discriminating power of combining multiple CSF α-syn species with classical Alzheimer’s disease biomarkers. The combination of CSF o-/t-α-syn, p-S129-α-syn and p-tau provided the best fitting predictive model for discriminating PD patients from controls. Moreover, CSF o-α-syn levels correlated significantly with the severity of PD motor symptoms (<i>r</i> = -0.37).</p><h3>Conclusion</h3><p dir="ltr">Our new ELISA assays can serve as research tools to address the unmet need for reliable CSF biomarkers for PD and related disorders.</p><h2>Other Information</h2><p dir="ltr">Published in: Molecular Neurodegeneration<br>License: <a href="https://creativecommons.org/licenses/by/4.0/deed.en" rel="noreferrer noopener" target="_blank">https://creativecommons.org/licenses/by/4.0/</a>  <br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s13024-016-0072-9" target="_blank">https://dx.doi.org/10.1186/s13024-016-0072-9</a></p>
eu_rights_str_mv openAccess
id Manara2_2526e5ccce6174b8f39b13bb190f455c
identifier_str_mv 10.1186/s13024-016-0072-9
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/27101698
publishDate 2016
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv CC BY 4.0
spelling Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s diseaseNour K. Majbour (8809316)Nishant N. Vaikath (2901785)Karin D. van Dijk (18891685)Mustafa T. Ardah (4858657)Shiji Varghese (291775)Louise B. Vesterager (19738231)Liliana P. Montezinho (19738234)Stephen Poole (607442)Bared Safieh-Garabedian (3554684)Takahiko Tokuda (105837)Charlotte E. Teunissen (7830647)Henk W. Berendse (8809328)Wilma D. J. van de Berg (8809325)Omar M. A. El-Agnaf (8809331)Biomedical and clinical sciencesNeurosciencesParkinson’s diseaseAlpha synucleinCerebrospinal fluid biomarkersAmyloid oligomersBiomarkers<h3>Background</h3><p dir="ltr">Despite decades of intensive research, to date, there is no accepted diagnosis for Parkinson’s disease (PD) based on biochemical analysis of blood or CSF. However, neurodegeneration in the brains of PD patients begins several years before the manifestation of the clinical symptoms, pointing to serious flaw/limitations in this approach.</p><h3>Results</h3><p dir="ltr">To explore the potential use of alpha-synuclein (α-syn) species as candidate biomarkers for PD, we generated specific antibodies directed against wide array of α-syn species, namely total-, oligomeric- and phosphorylated-Ser129-α-syn (t-, o- and p-S129-α-syn). Next we sought to employ our antibodies to develop highly specific ELISA assays to quantify α-syn species in biological samples. Finally we verified the usefulness of our assays in CSF samples from 46 PD patients and 48 age-matched healthy controls. We also assessed the discriminating power of combining multiple CSF α-syn species with classical Alzheimer’s disease biomarkers. The combination of CSF o-/t-α-syn, p-S129-α-syn and p-tau provided the best fitting predictive model for discriminating PD patients from controls. Moreover, CSF o-α-syn levels correlated significantly with the severity of PD motor symptoms (<i>r</i> = -0.37).</p><h3>Conclusion</h3><p dir="ltr">Our new ELISA assays can serve as research tools to address the unmet need for reliable CSF biomarkers for PD and related disorders.</p><h2>Other Information</h2><p dir="ltr">Published in: Molecular Neurodegeneration<br>License: <a href="https://creativecommons.org/licenses/by/4.0/deed.en" rel="noreferrer noopener" target="_blank">https://creativecommons.org/licenses/by/4.0/</a>  <br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s13024-016-0072-9" target="_blank">https://dx.doi.org/10.1186/s13024-016-0072-9</a></p>2016-01-19T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s13024-016-0072-9https://figshare.com/articles/journal_contribution/Oligomeric_and_phosphorylated_alpha-synuclein_as_potential_CSF_biomarkers_for_Parkinson_s_disease/27101698CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/271016982016-01-19T03:00:00Z
spellingShingle Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease
Nour K. Majbour (8809316)
Biomedical and clinical sciences
Neurosciences
Parkinson’s disease
Alpha synuclein
Cerebrospinal fluid biomarkers
Amyloid oligomers
Biomarkers
status_str publishedVersion
title Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease
title_full Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease
title_fullStr Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease
title_full_unstemmed Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease
title_short Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease
title_sort Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease
topic Biomedical and clinical sciences
Neurosciences
Parkinson’s disease
Alpha synuclein
Cerebrospinal fluid biomarkers
Amyloid oligomers
Biomarkers