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.

Original languageEnglish
Pages (from-to)1460-1477
Number of pages18
JournalAnnals of Clinical and Translational Neurology
Issue number12
StatePublished - Dec 2018


FundersFunder number
Alzheimer’s Disease Cooperative Study
Biotie Therapeutics
Eli Lilly & Co.
F. Hoffman-La Roche, Ltd.
GE Medical
Michael J Fox Foundation
Northwestern Foundation
Orion Pharma
Parkinson Fonds Deutschland
Sage Bionetworks
Stifterverband fu€r die deutsche Wissenschaft
University Medical Center Goettingen
Waggoner Center for Alcohol/Addiction Research
National Institutes of Health
U.S. Department of Defense
National Heart, Lung, and Blood Institute
National Institute of Neurological Disorders and Stroke
Michael J. Fox Foundation for Parkinson's Research
Boehringer Ingelheim
National Park Foundation
Eli Lilly and Company
North Carolina GlaxoSmithKline Foundation
CHDI Foundation
Teva Pharmaceutical Industries
GE Healthcare
University of Pennsylvania
Takeda Pharmaceuticals U.S.A.
Bristol-Myers Squibb Canada
Novartis Pharmaceuticals Corporation
University of Texas at Austin
Parkinson’s Disease Foundation of India
School of Public Health, University of California Berkeley
Sanofi Genzyme
ACADIA Pharmaceuticals
Avid Radiopharmaceuticals
Roche Diagnostics
European Commission
Bundesministerium für Bildung und Forschung
Eisai Incorporated
Bayer Schering
H. Lundbeck A/S
Deutsche Parkinson Vereinigung
Desitin Arzneimittel


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