TY - JOUR
T1 - The Parkinson's progression markers initiative (PPMI)
T2 - establishing a PD biomarker cohort
AU - Marek, Kenneth
AU - Chowdhury, Sohini
AU - Siderowf, Andrew
AU - Lasch, Shirley
AU - Coffey, Christopher S.
AU - Caspell-Garcia, Chelsea
AU - Simuni, Tanya
AU - Jennings, Danna
AU - Tanner, Caroline M.
AU - Trojanowski, John Q.
AU - Shaw, Leslie M.
AU - Seibyl, John
AU - Schuff, Norbert
AU - Singleton, Andrew
AU - Kieburtz, Karl
AU - Toga, Arthur W.
AU - Mollenhauer, Brit
AU - Galasko, Doug
AU - Chahine, Lana M.
AU - Weintraub, Daniel
AU - Foroud, Tatiana
AU - Tosun-Turgut, Duygu
AU - Poston, Kathleen
AU - Arnedo, Vanessa
AU - Frasier, Mark
AU - Sherer, Todd
AU - Parkinson's Progression Markers Initiative
AU - Bressman, Susan
AU - Merchant, Kalpana M.
AU - Poewe, Werner
AU - Kopil, Catherine
AU - Naito, Anna
AU - Dorsey, Ray
AU - Casaceli, Cynthia
AU - Daegele, Nichole
AU - Albani, Justin
AU - Uribe, Liz
AU - Foster, Eric
AU - Long, Jeff
AU - Seedorff, Nick
AU - Crawford, Karen
AU - Smith, Danielle Elise
AU - Casalin, Paola
AU - Malferrari, Giulia
AU - Halter, Cheryl
AU - Heathers, Laura
AU - Russell, David
AU - Factor, Stewart
AU - Hogarth, Penelope
AU - Amara, Amy
AU - Hauser, Robert
AU - Jankovic, Joseph
AU - Stern, Matthew
AU - Hu, Shu-Ching
AU - Todd, Gretchen
AU - Saunders-Pullman, Rachel
AU - Richard, Irene
AU - Saint-Hilaire, Marie H.
AU - Seppi, Klaus
AU - Shill, Holly
AU - Fernandez, Hubert
AU - Trenkwalder, Claudia
AU - Oertel, Wolfgang
AU - Berg, Daniela
AU - Brockman, Kathrin
AU - Wurster, Isabel
AU - Rosenthal, Liana
AU - Tai, Yen
AU - Pavese, Nicola
AU - Barone, Paolo
AU - Isaacson, Stuart
AU - Espay, Alberto
AU - Rowe, Dominic
AU - Brandabur, Melanie
AU - Tetrud, James
AU - Liang, Grace
AU - Iranzo, Alex
AU - Tolosa, Eduardo
AU - Marder, Karen
AU - de Arriba Sanchez, Maria
AU - Stefanis, Leonidis
AU - Marti, Maria Jose
AU - Martinez, Javier Ruiz
AU - Corvol, Jean-Christophe
AU - Assly, Jan O.
AU - Brillman, Salima
AU - Giladi, Nir
AU - Smejdir, Debra
AU - Pelaggi, Julia
AU - Kausar, Farah
AU - Rees, Linda
AU - Sommerfield, Barbara
AU - Cresswell, Madeline
AU - Blair, Courtney
AU - Williams, Karen
AU - Zimmerman, Grace
AU - Guthrie, Stephanie
AU - Rawlins, Ashlee
AU - Donharl, Leigh
AU - Hunter, Christine
AU - Tran, Baochan
AU - Darin, Abigail
AU - Venkov, Heli
AU - Thomas, Cathi-Ann
AU - James, Raymond
AU - Heim, Beatrice
AU - Deritis, Paul
AU - Sprenger, Fabienne
AU - Raymond, Deborah
AU - Willeke, Diana
AU - Obradov, Zoran
AU - Mule, Jennifer
AU - Monahan, Nancy
AU - Gauss, Katharina
AU - Fontaine, Deborah
AU - Szpak, Daniel
AU - McCoy, Arita
AU - Dunlop, Becky
AU - Payne, Laura Marie
AU - Ainscough, Susan
AU - Carvajal, Lisbeth
AU - Silverstein, Rebecca
AU - Espay, Kristy
AU - Ranola, Madelaine
AU - Rezola, Elisabet Mondragon
AU - Santana, Helen Mejia
AU - Stamelou, Maria
AU - Garrido, Alicia
AU - Carvalho, Stephanie
AU - Kristiansen, Anne Grete
AU - Specketer, Krista
AU - Mirlman, Anat
AU - Facheris, Maurizio
AU - Soares, Holly
AU - Mintun, Mark A.
AU - Cedarbaum, Jesse
AU - Taylor, Peggy
AU - Slieker, Lawrence
AU - McBride, Brian
AU - Watson, Colin
AU - Montagut, Etienne
AU - Sheikh, Zulfiqar Haider
AU - Bingol, Baris
AU - Forrat, Remi
AU - Sardi, Pablo
AU - Fischer, Tanya
AU - Reith, Alastair D.
AU - Egebjerg, Jan
AU - Larsen, Lone Frydelund
AU - Breysse, Nathalie
AU - Meulien, Didier
AU - Saba, Barbara
AU - Kiyasova, Vera
AU - Min, Chris
AU - McAvoy, Thomas
AU - Umek, Robert
AU - Iredale, Philip
AU - Edgerton, Jeremy
AU - De Santi, Susan
AU - Czech, Christian
AU - Boess, Frank
AU - Sevigny, Jeffrey
AU - Kremer, Thomas
AU - Grachev, Igor
AU - Avbersek, Andreja
AU - Muglia, Pierandrea
AU - Stewart, Alexandra
AU - Prashad, Rene
AU - Taucher, Johannes
AU - Wilson, Renee
AU - Standaert, David
AU - Linder, Carly
AU - Baca, Marne
N1 - Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2018/12
Y1 - 2018/12
N2 - Objective: The Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials. Methods: A total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org. Results: Approximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS-UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α-synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t-tau (45/53) and p-tau (16/18) were reduced in PD versus HC (P < 0.01),. Interpretation: PPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials.
AB - Objective: The Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials. Methods: A total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org. Results: Approximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS-UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α-synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t-tau (45/53) and p-tau (16/18) were reduced in PD versus HC (P < 0.01),. Interpretation: PPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials.
UR - http://www.scopus.com/inward/record.url?scp=85055893238&partnerID=8YFLogxK
U2 - 10.1002/acn3.644
DO - 10.1002/acn3.644
M3 - Article
C2 - 30564614
AN - SCOPUS:85055893238
SN - 2328-9503
VL - 5
SP - 1460
EP - 1477
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
IS - 12
ER -