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

the Parkinson's Progression Markers Initiative

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 (US)
JournalAnnals of Clinical and Translational Neurology
DOIs
StateAccepted/In press - Jan 1 2018

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Parkinson Disease
Biomarkers
Dopamine Plasma Membrane Transport Proteins
Cerebrospinal Fluid
Synucleins
Corpus Striatum
Hypokinesia
Putamen
Tremor
Single-Photon Emission-Computed Tomography
Observational Studies
Disease Progression

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort. / the Parkinson's Progression Markers Initiative.

In: Annals of Clinical and Translational Neurology, 01.01.2018.

Research output: Contribution to journalArticle

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title = "The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort",
abstract = "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.",
author = "{the Parkinson's Progression Markers Initiative} and Kenneth Marek and Sohini Chowdhury and Andrew Siderowf and Shirley Lasch and Coffey, {Christopher S.} and Chelsea Caspell-Garcia and Tanya Simuni and Danna Jennings and Tanner, {Caroline M.} and Trojanowski, {John Q.} and Shaw, {Leslie M.} and John Seibyl and Norbert Schuff and Andrew Singleton and Karl Kieburtz and Toga, {Arthur W.} and Brit Mollenhauer and Doug Galasko and Chahine, {Lana M.} and Daniel Weintraub and Tatiana Foroud and Duygu Tosun-Turgut and Kathleen Poston and Vanessa Arnedo and Mark Frasier and Todd Sherer and Susan Bressman and M. Merchant and Werner Poewe and Catherine Kopil and Anna Naito and Ray Dorsey and Cynthia Casaceli and Nichole Daegele and Justin Albani and Liz Uribe and Eric Foster and Jeff Long and Nick Seedorff and Karen Crawford and Danielle Smith and Paola Casalin and Giulia Malferrari and Cheryl Halter and Laura Heathers and David Russell and Stewart Factor and Penelope Hogarth and Amy Amara and Robert Hauser",
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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 - Hauser, Robert

PY - 2018/1/1

Y1 - 2018/1/1

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

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