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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Kang, Ju-Hee, Irwin, David J, Chen-Plotkin, Alice S, Siderowf, Andrew, Caspell, Chelsea, Coffey, Christopher S, Waligórska, Teresa, Taylor, Peggy, Pan, Sarah, Frasier, Mark, Marek, Kenneth, Kieburtz, Karl, Jennings, Danna, Simuni, Tanya, Tanner, Caroline M, Singleton, Andrew, Toga, Arthur W, Chowdhury, Sohini, Mollenhauer, Brit, Trojanowski, John Q, Shaw, Leslie M, Lasch, Shirley, Flagg, Emily, Poewe, Werner, Sherer, Todd, Meunier, Claire, Rudolph, Alice, Casaceli, Cindy, Seibyl, John, Mendick, Susan, Schuff, Norbert, Uribe, Liz, Yankey, Jon, Crawford, Karen, Scutti, Alison, Casalin, Paola, Malferrari, Giulia, Hawkins, Keith, Russell, David, Leary, Laura, Factor, Stewart, Sommerfeld, Barbara, Hogarth, Penelope, Pighetti, Emily, Williams, Karen, Standaert, David, Guthrie, Stephanie, Hauser, Robert, Jankovic, Joseph, Hunter, Christine, Stern, Matthew, Darin, Abigail, Leverenz, Jim, Baca, Marne, Frank, Sam, Thomas, Cathi-Ann, Richard, Irene, Deeley, Cheryl, Rees, Linda, Sprenger, Fabienne, Oertel, Wolfgang, Willeke, Diana, Shill, Holly, Fernandez, Hubert, Mule, Jennifer, Berg, Daniela, Gauss, Katharina, Galasko, Douglas, Fontaine, Deborah, Mari, Zoltan, McCoy, Arita, Brooks, David, Shah, Bina, Barone, Paolo, Isaacson, Stuart, James, Angela, Espay, Alberto, Espay, Kristy, Rowe, Dominic, and Ranola, Madelaine
- Subjects
Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Neurosciences ,Aging ,Neurodegenerative ,Brain Disorders ,Dementia ,Acquired Cognitive Impairment ,Parkinson's Disease ,Clinical Research ,2.1 Biological and endogenous factors ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,4.1 Discovery and preclinical testing of markers and technologies ,Aetiology ,Neurological ,Amyloid beta-Peptides ,Case-Control Studies ,Cohort Studies ,Female ,Humans ,Male ,Memory ,Middle Aged ,Movement ,Neuropsychological Tests ,Parkinson Disease ,Peptide Fragments ,Phosphorylation ,Regression Analysis ,Severity of Illness Index ,Statistics as Topic ,Threonine ,Verbal Learning ,alpha-Synuclein ,tau Proteins ,Parkinson's Progression Markers Initiative - Abstract
ImportanceWe 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.ObjectiveTo 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.Design, setting, and participantsCross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort.Main outcomes and measuresThe 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.ResultsSlightly, 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 and relevanceIn 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
- Published
- 2013