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Association of Cerebrospinal Fluid β-Amyloid 1-42, T-tau, P-tau 181 , and α-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease

2013; American Medical Association; Linguagem: Inglês

10.1001/jamaneurol.2013.3861

2168-6157

Ju‐Hee Kang, David J. Irwin, Alice Chen‐Plotkin, Andrew Siderowf, Chelsea Caspell, Christopher S. Coffey, Teresa Waligórska, Peggy Taylor, Sarah Pan, Mark Frasier, Kenneth Marek, Karl Kieburtz, Danna Jennings, Tanya Simuni, Caroline M. Tanner, Andrew Singleton, Arthur W. Toga, Sohini Chowdhury, Brit Mollenhauer, John Q. Trojanowski, Leslie M. Shaw, Shirley Lasch, Emily Flagg, Werner Poewe, Todd Sherer, Claire C. Meunier, Alice Rudolph, Cindy Casaceli, John Seibyl, Susan Mendick, Norbert Schuff, Liz Uribe, Jon Yankey, Karen Crawford, Alison Scutti, Paola Casalin, Giulia Malferrari, Keith A. Hawkins, David Russell, Laura Leary, Stewart A. Factor, Barbara Sommerfeld, Penelope Hogarth, Emily Pighetti, Karen Williams, David G. Standaert, Stephanie Guthrie, Robert A. Hauser, Joseph Jankovic, Christine Hunter, Matthew Stern, Abigail Darin, James B. Leverenz, Marne Baca, Sam Frank, Cathi-Ann Thomas, Irene Hegeman Richard, Cheryl Deeley, Linda Rees, Fabienne Sprenger, Wolfgang H. Oertel, Diana Willeke, Holly A. Shill, Hubert H. Fernandez, Jennifer Mule, Daniela Berg, Katharina Gauss, Douglas Galasko, Deborah Fontaine, Zoltán Mari, Arita McCoy, David J. Brooks, Bina Shah, Paolo Barone, Stuart Isaacson, Angela James, Alberto J. Espay, Kristy J. Espay, Dominic B. Rowe, Madelaine Ranola,

Alzheimer's disease research and treatments

Importance 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-tau 181 ], 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 (Aβ1-42, T-tau, and P-tau 181 ; 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-tau 181 , 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-tau 181 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-tau 181 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-tau 181 . Conclusions and Relevance In this first report of CSF biomarkers in PPMI study subjects, we found that measures of CSF Aβ1-42, T-tau, P-tau 181 , 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.