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

Nour K. Majbour; Nishant N. Vaikath; Karin van Dijk; Mustafa T. Ardah; Shiji Varghese; Louise B. Vesterager; Liliana P. Montezinho; Stephen Poole; Bared Safieh-Garabedian; Takahiko Tokuda; Charlotte E. Teunissen; Hendrik Berendse; Wilma D. J. van de Berg; Omar M. A. El-Agnaf

doi:https://doi.org/10.1186/s13024-016-0072-9

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

Nour K. Majbour, Nishant N. Vaikath, Karin van Dijk, Mustafa T. Ardah, Shiji Varghese, Louise B. Vesterager, Liliana P. Montezinho, Stephen Poole, Bared Safieh-Garabedian, Takahiko Tokuda, Charlotte E. Teunissen, Hendrik Berendse, Wilma D. J. van de Berg, Omar M. A. El-Agnaf

Research output: Contribution to journal › Article › Academic › peer-review

184 Citations (Scopus)

Abstract

Background
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.

Results
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 (r = -0.37).

Conclusion
Our new ELISA assays can serve as research tools to address the unmet need for reliable CSF biomarkers for PD and related disorders.

Original language	English
Article number	7
Journal	Molecular Neurodegeneration
Volume	11
DOIs	https://doi.org/10.1186/s13024-016-0072-9
Publication status	Published - 19 Jan 2016

Keywords

Alpha synuclein
Amyloid oligomers
Biomarkers
Cerebrospinal fluid biomarkers
Parkinson's disease

Access to Document

https://doi.org/10.1186/s13024-016-0072-9

Cite this

Majbour, N. K., Vaikath, N. N., van Dijk, K., Ardah, M. T., Varghese, S., Vesterager, L. B., Montezinho, L. P., Poole, S., Safieh-Garabedian, B., Tokuda, T., Teunissen, C. E., Berendse, H., van de Berg, W. D. J., & El-Agnaf, O. M. A. (2016). Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson's disease. Molecular Neurodegeneration, 11, Article 7. https://doi.org/10.1186/s13024-016-0072-9

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title = "Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson's disease",

abstract = "BackgroundDespite decades of intensive research, to date, there is no accepted diagnosis for Parkinson{\textquoteright}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.ResultsTo 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{\textquoteright}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 (r = -0.37).ConclusionOur new ELISA assays can serve as research tools to address the unmet need for reliable CSF biomarkers for PD and related disorders.",

keywords = "Alpha synuclein, Amyloid oligomers, Biomarkers, Cerebrospinal fluid biomarkers, Parkinson's disease",

author = "Majbour, {Nour K.} and Vaikath, {Nishant N.} and {van Dijk}, Karin and Ardah, {Mustafa T.} and Shiji Varghese and Vesterager, {Louise B.} and Montezinho, {Liliana P.} and Stephen Poole and Bared Safieh-Garabedian and Takahiko Tokuda and Teunissen, {Charlotte E.} and Hendrik Berendse and {van de Berg}, {Wilma D. J.} and El-Agnaf, {Omar M. A.}",

year = "2016",

month = jan,

day = "19",

doi = "https://doi.org/10.1186/s13024-016-0072-9",

language = "English",

volume = "11",

journal = "Molecular Neurodegeneration",

issn = "1750-1326",

publisher = "BioMed Central",

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Majbour, NK, Vaikath, NN, van Dijk, K, Ardah, MT, Varghese, S, Vesterager, LB, Montezinho, LP, Poole, S, Safieh-Garabedian, B, Tokuda, T, Teunissen, CE , Berendse, H , van de Berg, WDJ & El-Agnaf, OMA 2016, 'Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson's disease', Molecular Neurodegeneration, vol. 11, 7. https://doi.org/10.1186/s13024-016-0072-9

TY - JOUR

T1 - Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson's disease

AU - Majbour, Nour K.

AU - Vaikath, Nishant N.

AU - van Dijk, Karin

AU - Ardah, Mustafa T.

AU - Varghese, Shiji

AU - Vesterager, Louise B.

AU - Montezinho, Liliana P.

AU - Poole, Stephen

AU - Safieh-Garabedian, Bared

AU - Tokuda, Takahiko

AU - Teunissen, Charlotte E.

AU - Berendse, Hendrik

AU - van de Berg, Wilma D. J.

AU - El-Agnaf, Omar M. A.

PY - 2016/1/19

Y1 - 2016/1/19

N2 - BackgroundDespite 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.ResultsTo 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 (r = -0.37).ConclusionOur new ELISA assays can serve as research tools to address the unmet need for reliable CSF biomarkers for PD and related disorders.

AB - BackgroundDespite 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.ResultsTo 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 (r = -0.37).ConclusionOur new ELISA assays can serve as research tools to address the unmet need for reliable CSF biomarkers for PD and related disorders.

KW - Alpha synuclein

KW - Amyloid oligomers

KW - Biomarkers

KW - Cerebrospinal fluid biomarkers

KW - Parkinson's disease

U2 - https://doi.org/10.1186/s13024-016-0072-9

DO - https://doi.org/10.1186/s13024-016-0072-9

M3 - Article

C2 - 26782965

SN - 1750-1326

VL - 11

JO - Molecular Neurodegeneration

JF - Molecular Neurodegeneration

M1 - 7

ER -