Association of Cerebrospinal Fluid ?-Amyloid 1-42, T-tau, P-tau181, and ?-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease.
IMPORTANCE We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and ?-synuclein, but not ?-amyloid 1-42 (A?1-42), 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 (A?1-42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181], and ?-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinsons Progression Markers Initiative (PPMI) study. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort. MAIN OUTCOMES AND MEASURES The CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (A?1-42, T-tau, and P-tau181; Innogenetics Inc) or by enzyme-linked immunosorbent assay (?-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 A?1-42, T-tau, P-tau181, ?-synuclein, and T-tau/A?1-42 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 A?1-42 and P-tau181 levels were associated with PD diagnosis and that decreased CSF T-tau and ?-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF A?1-42 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 ?-synuclein with the levels of T-tau and P-tau181. CONCLUSIONS AND RELEVANCE In this first report of CSF biomarkers in PPMI study subjects, we found that measures of CSF A?1-42, T-tau, P-tau181, and ?-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.