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Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls

2017; Lippincott Williams & Wilkins; Volume: 89; Issue: 19 Linguagem: Inglês

10.1212/wnl.0000000000004609

1526-632X

Brit Mollenhauer, Chelsea Caspell‐Garcia, Christopher S. Coffey, Peggy Taylor, Leslie M. Shaw, John Q. Trojanowski, Andy Singleton, Mark Frasier, Kenneth Marek, Douglas Galasko, Kenneth Marek, Danna Jennings, Shirley Lasch, Caroline M. Tanner, Tanya Simuni, Christopher S. Coffey, Karl Kieburtz, Renée Wilson, Werner Poewe, Brit Mollenhauer, Tatiana Foroud, Todd Sherer, Sohini Chowdhury, Mark Frasier, Catherine Kopil, Vanessa Arnedo, Alice Rudolph, Cynthia Casaceli, John Seibyl, Susan Mendick, Norbert Schuff, Chelsea Caspell, Liz Uribe, Eric D. Foster, Katherine Gloer, Jon Yankey, Arthur W. Toga, Karen Crawford, Paola Casalin, Giulia Malferrari, Brit Mollenhauer, Douglas Galasko, Andrew Singleton, Keith A. Hawkins, David H. Russell, Stewart A. Factor, Penelope Hogarth, David G. Standaert, Robert A. Hauser, Joseph Jankovic, Matthew Stern, Lana M. Chahine, James B. Leverenz, Samuel Frank, Irene Hegeman Richard, Klaus Seppi, Holly A. Shill, Hubert Fernandez, Daniela Berg, Isabel Wurster, Douglas Galasko, Zoltan Mari, David J. Brooks, Nicola Pavese, Paolo Barone, Stuart Isaacson, Alberto J. Espay, Dominic B. Rowe, Melanie Brandabur, James W. Tetrud, Grace Liang, Álex Iranzo, Eduardo Tolosa, Laura Leary, C Riordan, Linda Rees, Alicia Portillo, Art Lenahan, Karen Williams, Stephanie Guthrie, Ashlee Brooke Rawlins, Sherry Harlan, Christine Hunter, Baochan Tran, Abigail Darin, Carly Linder, Marne Baca, Heli Venkov, Cathi-Ann Thomas, Raymond James, Cheryl Deeley, Courtney Bishop, Fabienne Sprenger, Diana Willeke, Sanja Obradov, Jennifer Mule, Nancy Monahan, Katharina Gauss, Deborah Fontaine, Christina Gigliotti, Arita McCoy, Becky Dunlop, Bina Shah, Ainscough Susan, Angela James, Rebecca A. Silverstein, Kristy J. Espay, Madelaine Ranola, Kenneth Marek, Principal Investigator, Danna Jennings, Shirley Lasch, Andrew Siderowf, Tanner Caroline, Tanya Simuni, Christopher S. Coffey, Karl Kieburtz, Emily Flagg, Sohini Chowdhury, Werner Poewe, Brit Mollenhauer, Todd Sherer, Mark Frasier, Claire C. Meunier, Alice Rudolph, Cindy Casaceli, John Seibyl, Principal Investigator, Susan Mendick, Norbert Schuff, Ying Zhang, Arthur W. Toga, Karen Crawford, Alison B. Ansbach, Pasquale De Blasio, Michele Piovella, John Q. Trojanowski, Les Shaw, Andrew Singleton, Keith A. Hawkins, J PsyDMichael, Jamie L. Eberling, Deborah W. Brooks, David H. Russell, Laura Leary, Stewart A. Factor, Barbara Sommerfeld, Penelope Hogarth, Emily Pighetti, Karen Williams, David G. Standaert, Stephanie Guthrie, Robert A. Hauser, Holly Delgado, Joseph Jankovic, Christine Hunter, Matthew Stern, Baochan Tran, James B. Leverenz, Marne Baca, Sam Frank, Cathi-Ann Thomas, Irene Hegeman Richard, Cheryl Deeley, Linda Rees, Fabienne Sprenger, Wolfgang H. Oertel, Elisabeth Lang, Holly A. Shill, Sanja Obradov, Hubert Fernandez, Adrienna Winters, Daniela Berg, Katharina Gauss, Douglas Galasko, Deborah Fontaine, Zoltan Mari, Melissa Gerstenhaber, David J. Brooks, Sophie Malloy, Paolo Barone, Katia Longo, Tom Comery, Bernard Ravina, Igor D. Grachev, Kim P. Gallagher, Michelle Collins, Katherine L. Widnell, Suzanne Ostrowizki, Paulo Fontoura, F. Laroche, Tony W. Ho, Johan Luthman, Marcel van der Brug, Alastair D. Reith, Peggy Taylor,

Alzheimer's disease research and treatments

To analyze longitudinal levels of CSF biomarkers in drug-naive patients with Parkinson disease (PD) and healthy controls (HC), examine the extent to which these biomarker changes relate to clinical measures of PD, and identify what may influence them.CSF α-synuclein (α-syn), total and phosphorylated tau (t- and p-tau), and β-amyloid 1-42 (Aβ42) were measured at baseline and 6 and 12 months in 173 patients with PD and 112 matched HC in the international multicenter Parkinson's Progression Marker Initiative. Baseline clinical and demographic variables, PD medications, neuroimaging, and genetic variables were evaluated as potential predictors of CSF biomarker changes.CSF biomarkers were stable over 6 and 12 months, and there was a small but significant increase in CSF Aβ42 in both patients with patients with PD and HC from baseline to 12 months. The t-tau remained stable. The p-tau increased marginally more in patients with PD than in HC. α-syn remained relatively stable in patients with PD and HC. Ratios of p-tau/t-tau increased, while t-tau/Aβ42 decreased over 12 months in patients with PD. CSF biomarker changes did not correlate with changes in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale motor scores or dopamine imaging. CSF α-syn levels at 12 months were lower in patients with PD treated with dopamine replacement therapy, especially dopamine agonists.These core CSF biomarkers remained stable over 6 and 12 months in patients with early PD and HC. PD medication use may influence CSF α-syn. Novel biomarkers are needed to better profile progressive neurodegeneration in PD.