Association of cerebrospinal fluid ß-amyloid 1-42, T-tau, P-tau181, and α-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 α-synuclein, but not ß-amyloid 1-42 (Aß1-42), 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 (Aß1-42, 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. 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 (Aß1-42, 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 Aß1-42, T-tau, P-tau181, α-synuclein, and T-tau/Aß1-42 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 Aß1-42 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 Aß1-42 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 AND RELEVANCE: In this first report of CSF biomarkers in PPMI study subjects,we found that measures of CSF Aß1-42, 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

Height, BMI, and pituitary volume in individuals with and without isolated cleft lip and/or palate.

INTRODUCTION: Individuals with isolated cleft lip and/or palate (ICLP) are often reported to be of shorter stature relative to peers, and the objective of this study was to explore the role of the pituitary in relationship to growth. METHODS: Fifty-five males and 32 females with ICLP were compared to 121 healthy males and 158 healthy females with respect to height and BMI. Magnetic resonance imaging (MRI) scans were obtained from all ICLP participants and 47% of healthy group participants. RESULTS: Males with ICLP were shorter than healthy males and had lower BMI. However, the trajectories for height and BMI did not differ between groups. Analyses in a separate sample of adult males suggested that height normalizes in males with ICLP in their early 30s. There were no differences in mean pituitary volume and pituitary trajectories between male groups. Females with ICLP were shorter than healthy females and also had slower growth rates. They did not differ in mean BMI or BMI trajectories. Furthermore, there were no differences in mean pituitary volume, or in pituitary trajectories. DISCUSSION: Our findings suggest that there are no gross morphological differences in pituitary volume in individuals with ICLP, although more subtle differences may exist.