TY - JOUR
T1 - The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort
AU - the Parkinson's Progression Markers Initiative
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 - Bressman, Susan
AU - Merchant, 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
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 - Marder, Karen
N1 - Publisher Copyright:
© 2018 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
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.
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U2 - 10.1002/acn3.644
DO - 10.1002/acn3.644
M3 - Article
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 -