title: Association of cerebrospinal fluid β-amyloid 1-42, T-tau, P-tau181, and α-synuclein levels with clinical features of drug-naive patients with early Parkinson disease.
abstract: OBJECTIVE
  We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1-42 (Aβ1-42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far.
  
  
  OBJECTIVE
  To evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (Aβ1-42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181], and α-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson's Progression Markers Initiative (PPMI) study.
  
  
  METHODS
  Cross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort.
  
  
  METHODS
  The CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (Aβ1-42, T-tau, and P-tau181; Innogenetics Inc) or by enzyme-linked immunosorbent assay (α-synuclein). Clinical features including diagnosis, demographic characteristics, motor, neuropsychiatric, and cognitive assessments, and DaTscan were systematically assessed according to the PPMI study protocol.
  
  
  RESULTS
  Slightly, but significantly, lower levels of Aβ1-42, T-tau, P-tau181, α-synuclein, and T-tau/Aβ1-42 were seen in subjects with PD compared with healthy controls but with a marked overlap between groups. Using multivariate regression analysis, we found that lower Aβ1-42 and P-tau181 levels were associated with PD diagnosis and that decreased CSF T-tau and α-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF Aβ1-42 and P-tau181 concentrations were associated with the postural instability-gait disturbance-dominant phenotype but not with the tremor-dominant or intermediate phenotype. Finally, we found a significant correlation of the levels of α-synuclein with the levels of T-tau and P-tau181.
  
  
  CONCLUSIONS
  In this first report of CSF biomarkers in PPMI study subjects,we found that measures of CSF Aβ1-42, T-tau, P-tau181, and α-synuclein have prognostic and diagnostic potential in early-stage PD. Further investigations using the entire PPMI cohort will test the predictive performance of CSF biomarkers for PD progression
authors: Ju-Hee
authors: JH
authors: Kang
authors: David J
authors: DJ
authors: Irwin
authors: Alice S
authors: AS
authors: Chen-Plotkin
authors: Andrew
authors: A
authors: Siderowf
authors: Chelsea
authors: C
authors: Caspell
authors: Christopher S
authors: CS
authors: Coffey
authors: Teresa
authors: T
authors: Waligórska
authors: Peggy
authors: P
authors: Taylor
authors: Sarah
authors: S
authors: Pan
authors: Mark
authors: M
authors: Frasier
authors: Kenneth
authors: K
authors: Marek
authors: Karl
authors: K
authors: Kieburtz
authors: Danna
authors: D
authors: Jennings
authors: Tanya
authors: T
authors: Simuni
authors: Caroline M
authors: CM
authors: Tanner
authors: Andrew
authors: A
authors: Singleton
authors: Arthur W
authors: AW
authors: Toga
authors: Sohini
authors: S
authors: Chowdhury
authors: Brit
authors: B
authors: Mollenhauer
authors: John Q
authors: JQ
authors: Trojanowski
authors: Leslie M
authors: LM
authors: Shaw
mesh_terms: D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009068:Movement / Q000502:physiology; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D012044:Regression Analysis; D012720:Severity of Illness Index; D013223:Statistics as Topic; D013912:Threonine / Q000378:metabolism*; D014706:Verbal Learning / Q000502:physiology; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D013912:Threonine
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