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 Weintraub; Tatiana Foroud; Duygu Tosun-Turgut; Kathleen Poston; Vanessa Arnedo; Mark Frasier; Todd Sherer; Parkinson's Progression Markers Initiative

doi:10.1002/acn3.644

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

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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, …

Annals of clinical and translational neurology, Vol.5(12), pp.1460-1477

12/2018

DOI: 10.1002/acn3.644

PMCID: PMC6292383

PMID: 30564614

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Abstract

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. 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. 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 ( < 0.03). Similarly, -tau (45/53) and -tau (16/18) were reduced in PD versus HC ( < 0.01). 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.

Details

Title: Subtitle: The Parkinson's progression markers initiative (PPMI) - establishing a PD biomarker cohort
Creators: Kenneth Marek - Institute for Neurodegenerative Disorders New Haven Connecticut
Sohini Chowdhury - The Michael J. Fox Foundation for Parkinson's Research New York New York
Andrew Siderowf - University of Pennsylvania Philadelphia Pennsylvania
Shirley Lasch - Institute for Neurodegenerative Disorders New Haven Connecticut
Christopher S Coffey - University of Iowa Iowa City Iowa
Chelsea Caspell-Garcia - University of Iowa Iowa City Iowa
Tanya Simuni - Northwestern University Chicago Illinois
Danna Jennings - Eli Lilly and Company New York New York
Caroline M Tanner - University of California San Francisco California
John Q Trojanowski - University of Pennsylvania Philadelphia Pennsylvania
Leslie M Shaw - University of Pennsylvania Philadelphia Pennsylvania
John Seibyl - Institute for Neurodegenerative Disorders New Haven Connecticut
Norbert Schuff - University of California San Francisco California
Andrew Singleton - National Institute on Aging NIH Bethesda Maryland
Karl Kieburtz - Clinical Trials Coordination Center University of Rochester Rochester New York
Arthur W Toga - National Institute on Aging NIH Bethesda Maryland
Brit Mollenhauer - Paracelsus-Elena Klinik Kassel Germany
Doug Galasko - University of California San Diego California
Lana M Chahine - University of Pennsylvania Philadelphia Pennsylvania
Daniel Weintraub - University of Pennsylvania Philadelphia Pennsylvania
Tatiana Foroud - Indiana University Indianapolis Indianapolis
Duygu Tosun-Turgut - University of California San Francisco California
Kathleen Poston - Stanford University Medical Center Stanford California
Vanessa Arnedo - The Michael J. Fox Foundation for Parkinson's Research New York New York
Mark Frasier - The Michael J. Fox Foundation for Parkinson's Research New York New York
Todd Sherer - The Michael J. Fox Foundation for Parkinson's Research New York New York
Parkinson's Progression Markers Initiative
Resource Type: Journal article
Publication Details: Annals of clinical and translational neurology, Vol.5(12), pp.1460-1477
DOI: 10.1002/acn3.644
PMID: 30564614
PMCID: PMC6292383
NLM abbreviation: Ann Clin Transl Neurol
ISSN: 2328-9503
eISSN: 2328-9503
Grant note: DOI: 10.13039/100004312, name: Eli Lilly and Company; DOI: 10.13039/100005614, name: Biogen; DOI: 10.13039/100011110, name: UCB; DOI: 10.13039/100006775, name: GE Healthcare; DOI: 10.13039/100000864, name: Michael J. Fox Foundation for Parkinson's Research; DOI: 10.13039/100004334, name: Merck; DOI: 10.13039/100004330, name: GlaxoSmithKline; DOI: 10.13039/100007054, name: Meso Scale Diagnostics; DOI: 10.13039/100004319, name: Pfizer; DOI: 10.13039/100006483, name: AbbVie
Language: English
Date published: 12/2018
Academic Unit: Biostatistics
Record Identifier: 9984214725702771

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