Cargando…

Phosphorylated α-synuclein in Parkinson’s disease: correlation depends on disease severity

INTRODUCTION: α-Synuclein (α-syn) is a key protein in Parkinson’s disease (PD), and one of its phosphorylated forms, pS129, is higher in PD patients than healthy controls. However, few studies have examined its levels in longitudinally collected cerebrospinal fluid (CSF) or in preclinical cases. In...

Descripción completa

Detalles Bibliográficos
Autores principales: Stewart, Tessandra, Sossi, Vesna, Aasly, Jan O, Wszolek, Zbigniew K, Uitti, Ryan J, Hasegawa, Kazuko, Yokoyama, Teruo, Zabetian, Cyrus P, Leverenz, James B, Stoessl, Alexander Jon, Wang, Yu, Ginghina, Carmen, Liu, Changqin, Cain, Kevin C, Auinger, Peggy, Kang, Un Jung, Jensen, Poul Henning, Shi, Min, Zhang, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362824/
https://www.ncbi.nlm.nih.gov/pubmed/25637461
http://dx.doi.org/10.1186/s40478-015-0185-3
_version_ 1782361848198201344
author Stewart, Tessandra
Sossi, Vesna
Aasly, Jan O
Wszolek, Zbigniew K
Uitti, Ryan J
Hasegawa, Kazuko
Yokoyama, Teruo
Zabetian, Cyrus P
Leverenz, James B
Stoessl, Alexander Jon
Wang, Yu
Ginghina, Carmen
Liu, Changqin
Cain, Kevin C
Auinger, Peggy
Kang, Un Jung
Jensen, Poul Henning
Shi, Min
Zhang, Jing
author_facet Stewart, Tessandra
Sossi, Vesna
Aasly, Jan O
Wszolek, Zbigniew K
Uitti, Ryan J
Hasegawa, Kazuko
Yokoyama, Teruo
Zabetian, Cyrus P
Leverenz, James B
Stoessl, Alexander Jon
Wang, Yu
Ginghina, Carmen
Liu, Changqin
Cain, Kevin C
Auinger, Peggy
Kang, Un Jung
Jensen, Poul Henning
Shi, Min
Zhang, Jing
author_sort Stewart, Tessandra
collection PubMed
description INTRODUCTION: α-Synuclein (α-syn) is a key protein in Parkinson’s disease (PD), and one of its phosphorylated forms, pS129, is higher in PD patients than healthy controls. However, few studies have examined its levels in longitudinally collected cerebrospinal fluid (CSF) or in preclinical cases. In this study, CSF and clinical data were contributed by >300 subjects from three cohorts (the longitudinal DATATOP cohort, a large cross-sectional cohort, and a cohort of LRRK2 mutation carriers). RESULTS: Consistent with our previous observation that CSF pS129 positively correlated with Unified Parkinson’s Disease Rating Scale (UPDRS) scores, CSF pS129 in the DATATOP cohort increased over approximately two years of disease progression (mean change 5.60 pg/ml, p = 0.050). Intriguingly, in the DATATOP cohort, pS129 negatively correlated with UPDRS scores at the baseline (R = −0.244, p = 0.017), but not final point, suggesting that this association may depend on disease stage. Reanalysis of our previous cohort with stratification by PD stage, and addition of a cohort of LRRK2 mutation carriers with very early/preclinical PD, supported the idea that the relationship between CSF pS129 and disease severity over a wider range of PD stages might be represented with a U-shaped curve, in which lower pS129 levels correlated with worse clinical condition at early stages, but better condition at later stages. CONCLUSION: The observation of a negative-to-positive transition of correlation of pS129 to disease severity as PD progresses could have profound impact on how pS129 is used as a biomarker clinically as well as in modeling PD experimentally.
format Online
Article
Text
id pubmed-4362824
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-43628242015-03-18 Phosphorylated α-synuclein in Parkinson’s disease: correlation depends on disease severity Stewart, Tessandra Sossi, Vesna Aasly, Jan O Wszolek, Zbigniew K Uitti, Ryan J Hasegawa, Kazuko Yokoyama, Teruo Zabetian, Cyrus P Leverenz, James B Stoessl, Alexander Jon Wang, Yu Ginghina, Carmen Liu, Changqin Cain, Kevin C Auinger, Peggy Kang, Un Jung Jensen, Poul Henning Shi, Min Zhang, Jing Acta Neuropathol Commun Research INTRODUCTION: α-Synuclein (α-syn) is a key protein in Parkinson’s disease (PD), and one of its phosphorylated forms, pS129, is higher in PD patients than healthy controls. However, few studies have examined its levels in longitudinally collected cerebrospinal fluid (CSF) or in preclinical cases. In this study, CSF and clinical data were contributed by >300 subjects from three cohorts (the longitudinal DATATOP cohort, a large cross-sectional cohort, and a cohort of LRRK2 mutation carriers). RESULTS: Consistent with our previous observation that CSF pS129 positively correlated with Unified Parkinson’s Disease Rating Scale (UPDRS) scores, CSF pS129 in the DATATOP cohort increased over approximately two years of disease progression (mean change 5.60 pg/ml, p = 0.050). Intriguingly, in the DATATOP cohort, pS129 negatively correlated with UPDRS scores at the baseline (R = −0.244, p = 0.017), but not final point, suggesting that this association may depend on disease stage. Reanalysis of our previous cohort with stratification by PD stage, and addition of a cohort of LRRK2 mutation carriers with very early/preclinical PD, supported the idea that the relationship between CSF pS129 and disease severity over a wider range of PD stages might be represented with a U-shaped curve, in which lower pS129 levels correlated with worse clinical condition at early stages, but better condition at later stages. CONCLUSION: The observation of a negative-to-positive transition of correlation of pS129 to disease severity as PD progresses could have profound impact on how pS129 is used as a biomarker clinically as well as in modeling PD experimentally. BioMed Central 2015-01-31 /pmc/articles/PMC4362824/ /pubmed/25637461 http://dx.doi.org/10.1186/s40478-015-0185-3 Text en © Stewart et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Stewart, Tessandra
Sossi, Vesna
Aasly, Jan O
Wszolek, Zbigniew K
Uitti, Ryan J
Hasegawa, Kazuko
Yokoyama, Teruo
Zabetian, Cyrus P
Leverenz, James B
Stoessl, Alexander Jon
Wang, Yu
Ginghina, Carmen
Liu, Changqin
Cain, Kevin C
Auinger, Peggy
Kang, Un Jung
Jensen, Poul Henning
Shi, Min
Zhang, Jing
Phosphorylated α-synuclein in Parkinson’s disease: correlation depends on disease severity
title Phosphorylated α-synuclein in Parkinson’s disease: correlation depends on disease severity
title_full Phosphorylated α-synuclein in Parkinson’s disease: correlation depends on disease severity
title_fullStr Phosphorylated α-synuclein in Parkinson’s disease: correlation depends on disease severity
title_full_unstemmed Phosphorylated α-synuclein in Parkinson’s disease: correlation depends on disease severity
title_short Phosphorylated α-synuclein in Parkinson’s disease: correlation depends on disease severity
title_sort phosphorylated α-synuclein in parkinson’s disease: correlation depends on disease severity
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362824/
https://www.ncbi.nlm.nih.gov/pubmed/25637461
http://dx.doi.org/10.1186/s40478-015-0185-3
work_keys_str_mv AT stewarttessandra phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT sossivesna phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT aaslyjano phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT wszolekzbigniewk phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT uittiryanj phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT hasegawakazuko phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT yokoyamateruo phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT zabetiancyrusp phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT leverenzjamesb phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT stoesslalexanderjon phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT wangyu phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT ginghinacarmen phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT liuchangqin phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT cainkevinc phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT auingerpeggy phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT kangunjung phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT jensenpoulhenning phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT shimin phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity
AT zhangjing phosphorylatedasynucleininparkinsonsdiseasecorrelationdependsondiseaseseverity