The Parkinson's progression markers initiative (PPMI): establishing a PD biomarker cohort

Kenneth Marek*, Sohini Chowdhury, Andrew Siderowf, Shirley Lasch, Christopher S. Coffey, Chelsea Caspell-Garcia, Tanya Simuni, Danna Jennings, Caroline M. Tanner, John Q. Trojanowski, Leslie M. Shaw, John Seibyl, Norbert Schuff, Andrew Singleton, Karl Kieburtz, Arthur W. Toga, Brit Mollenhauer, Doug Galasko, Lana M. Chahine, Daniel WeintraubTatiana Foroud, Duygu Tosun-Turgut, Kathleen Poston, Vanessa Arnedo, Mark Frasier, Todd Sherer, Parkinson's Progression Markers Initiative

*Corresponding author for this work

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    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 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.

    Original languageEnglish
    Pages (from-to)1460-1477
    Number of pages18
    JournalAnnals of Clinical and Translational Neurology
    Issue number12
    Early online date31 Oct 2018
    Publication statusPublished - Dec 2018

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    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.


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