1. 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
- Author
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Alberto J. Espay, David J. Irwin, Arita McCoy, Madelaine Ranola, Giulia Malferrari, Angela James, Stuart Isaacson, Caroline M. Tanner, Peggy Taylor, Laura Leary, Emily Pighetti, Abigail Darin, Brit Mollenhauer, Christine Hunter, Sohini Chowdhury, Dominic B. Rowe, Danna Jennings, Andrew Siderowf, Zoltan Mari, Jon W. Yankey, Shirley Lasch, Hubert H. Fernandez, Arthur W. Toga, Ju-Hee Kang, Robert A. Hauser, Leslie M. Shaw, Daniela Berg, Diana Willeke, Katharina Gauss, John Seibyl, Keith A. Hawkins, David Standaert, Liz Uribe, Kristy J. Espay, Karen Williams, Holly A. Shill, Alice Chen-Plotkin, Sam Frank, Paola Casalin, Douglas Galasko, Werner Poewe, Cindy Casaceli, Fabienne Sprenger, Karen Crawford, Wolfgang Oertel, Joseph Jankovic, Andrew B. Singleton, Alison Scutti, Paolo Barone, Sarah Pan, Deborah Fontaine, Alice Rudolph, Barbara Sommerfeld, David Brooks, Bina Shah, Teresa Waligorska, James B. Leverenz, Matthew B. Stern, Stewart A. Factor, Karl Kieburtz, Christopher S. Coffey, John Q. Trojanowski, Penelope Hogarth, Kenneth Marek, Norbert Schuff, Susan Mendick, Linda Rees, Cathi-Ann Thomas, Marne Baca, Todd Sherer, Mark Frasier, Tanya Simuni, Stephanie Guthrie, David W. Russell, Claire Meunier, Jennifer Mule, Cheryl Deeley, Emily Flagg, Irene Richard, and Chelsea Caspell
- Subjects
Male ,Threonine ,medicine.medical_specialty ,Movement ,Statistics as Topic ,tau Proteins ,Neuropsychological Tests ,Verbal learning ,Severity of Illness Index ,Gastroenterology ,Article ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cerebrospinal fluid ,Memory ,Internal medicine ,mental disorders ,Severity of illness ,medicine ,Humans ,Phosphorylation ,030304 developmental biology ,Alpha-synuclein ,0303 health sciences ,Amyloid beta-Peptides ,business.industry ,Case-control study ,Parkinson Disease ,Middle Aged ,Verbal Learning ,Peptide Fragments ,3. Good health ,Drug-naïve ,chemistry ,Case-Control Studies ,Cohort ,Immunology ,alpha-Synuclein ,Regression Analysis ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,medicine.drug ,Cohort study - Abstract
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.
- Published
- 2013
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