title: Phosphorylated α-synuclein in Parkinson's disease: correlation depends on disease severity.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: Tessandra
authors: T
authors: Stewart
authors: Vesna
authors: V
authors: Sossi
authors: Jan O
authors: JO
authors: Aasly
authors: Zbigniew K
authors: ZK
authors: Wszolek
authors: Ryan J
authors: RJ
authors: Uitti
authors: Kazuko
authors: K
authors: Hasegawa
authors: Teruo
authors: T
authors: Yokoyama
authors: Cyrus P
authors: CP
authors: Zabetian
authors: James B
authors: JB
authors: Leverenz
authors: Alexander Jon
authors: AJ
authors: Stoessl
authors: Yu
authors: Y
authors: Wang
authors: Carmen
authors: C
authors: Ginghina
authors: Changqin
authors: C
authors: Liu
authors: Kevin C
authors: KC
authors: Cain
authors: Peggy
authors: P
authors: Auinger
authors: Un Jung
authors: UJ
authors: Kang
authors: Poul Henning
authors: PH
authors: Jensen
authors: Min
authors: M
authors: Shi
authors: Jing
authors: J
authors: Zhang
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D010766:Phosphorylation; D049268:Positron-Emission Tomography; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012372:ROC Curve; D012720:Severity of Illness Index; D013223:Statistics as Topic; D013997:Time Factors; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051844:alpha-Synuclein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
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