TY - JOUR
T1 - Phosphorylated α-synuclein in Parkinson's disease
T2 - correlation depends on disease severity
AU - Stewart, Tessandra
AU - Sossi, Vesna
AU - Aasly, Jan O.
AU - Wszolek, Zbigniew K.
AU - Uitti, Ryan J.
AU - Hasegawa, Kazuko
AU - Yokoyama, Teruo
AU - Zabetian, Cyrus P.
AU - Leverenz, James B.
AU - Stoessl, Alexander Jon
AU - Wang, Yu
AU - Ginghina, Carmen
AU - Liu, Changqin
AU - Cain, Kevin C.
AU - Auinger, Peggy
AU - Kang, Un Jung
AU - Jensen, Poul Henning
AU - Shi, Min
AU - Zhang, Jing
N1 - Funding Information:
We deeply appreciate the donation of CSF and participation by subjects in this study. This work was supported by the Michael J Fox Foundation, the Parkinson Study Group, and the NIH (NIA: R01 AG033398; NIEHS: P42 ES004696-5897, P30 ES007033-6364, R01 ES016873, R01 ES019277 and T32 ES015459; NINDS: R01 NS057567, R01 NS065070, P50 NS062684-6221, P50 NS072187, and U01 NS082137).
PY - 2015/1/31
Y1 - 2015/1/31
N2 - 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.
AB - 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.
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U2 - 10.1186/s40478-015-0185-3
DO - 10.1186/s40478-015-0185-3
M3 - Article
C2 - 25637461
AN - SCOPUS:85017330543
SN - 2051-5960
VL - 3
SP - 7
JO - Acta Neuropathologica Communications
JF - Acta Neuropathologica Communications
ER -