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

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

Research output: Contribution to journal › Article › peer-review

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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 language	English
Pages (from-to)	1460-1477
Number of pages	18
Journal	Annals of Clinical and Translational Neurology
Volume	5
Issue number	12
Early online date	31 Oct 2018
DOIs	https://doi.org/10.1002/acn3.644
Publication status	Published - 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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10.1002/acn3.644

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Marek, K., Chowdhury, S., Siderowf, A., Lasch, S., Coffey, C. S., Caspell-Garcia, C., Simuni, T., Jennings, D., Tanner, C. M., Trojanowski, J. Q., Shaw, L. M., Seibyl, J., Schuff, N., Singleton, A., Kieburtz, K., Toga, A. W., Mollenhauer, B., Galasko, D., Chahine, L. M., ... Parkinson's Progression Markers Initiative (2018). The Parkinson's progression markers initiative (PPMI): establishing a PD biomarker cohort. Annals of Clinical and Translational Neurology, 5(12), 1460-1477. https://doi.org/10.1002/acn3.644

@article{54b4d6ab45004b7f83275a8cc68a0b44,

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 = "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 {Parkinson's Progression Markers Initiative} and Susan Bressman and Merchant, {Kalpana M.} 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 Smith, {Danielle Elise} 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 and Joseph Jankovic and Matthew Stern and Shu-Ching Hu and Gretchen Todd and Rachel Saunders-Pullman and Irene Richard and Saint-Hilaire, {Marie H.} and Klaus Seppi and Holly Shill and Hubert Fernandez and Claudia Trenkwalder and Wolfgang Oertel and Daniela Berg and Kathrin Brockman and Isabel Wurster and Liana Rosenthal and Yen Tai and Nicola Pavese and Paolo Barone and Stuart Isaacson and Alberto Espay and Dominic Rowe and Melanie Brandabur and James Tetrud and Grace Liang and Alex Iranzo and Eduardo Tolosa and Karen Marder and {de Arriba Sanchez}, Maria and Leonidis Stefanis and Marti, {Maria Jose} and Martinez, {Javier Ruiz} and Jean-Christophe Corvol and Assly, {Jan O.} and Salima Brillman and Nir Giladi and Debra Smejdir and Julia Pelaggi and Farah Kausar and Linda Rees and Barbara Sommerfield and Madeline Cresswell and Courtney Blair and Karen Williams and Grace Zimmerman and Stephanie Guthrie and Ashlee Rawlins and Leigh Donharl and Christine Hunter and Baochan Tran and Abigail Darin and Heli Venkov and Cathi-Ann Thomas and Raymond James and Beatrice Heim and Paul Deritis and Fabienne Sprenger and Deborah Raymond and Diana Willeke and Zoran Obradov and Jennifer Mule and Nancy Monahan and Katharina Gauss and Deborah Fontaine and Daniel Szpak and Arita McCoy and Becky Dunlop and Payne, {Laura Marie} and Susan Ainscough and Lisbeth Carvajal and Rebecca Silverstein and Kristy Espay and Madelaine Ranola and Rezola, {Elisabet Mondragon} and Santana, {Helen Mejia} and Maria Stamelou and Alicia Garrido and Stephanie Carvalho and Kristiansen, {Anne Grete} and Krista Specketer and Anat Mirlman and Maurizio Facheris and Holly Soares and Mintun, {Mark A.} and Jesse Cedarbaum and Peggy Taylor and Lawrence Slieker and Brian McBride and Colin Watson and Etienne Montagut and Sheikh, {Zulfiqar Haider} and Baris Bingol and Remi Forrat and Pablo Sardi and Tanya Fischer and Reith, {Alastair D.} and Jan Egebjerg and Larsen, {Lone Frydelund} and Nathalie Breysse and Didier Meulien and Barbara Saba and Vera Kiyasova and Chris Min and Thomas McAvoy and Robert Umek and Philip Iredale and Jeremy Edgerton and {De Santi}, Susan and Christian Czech and Frank Boess and Jeffrey Sevigny and Thomas Kremer and Igor Grachev and Andreja Avbersek and Pierandrea Muglia and Alexandra Stewart and Rene Prashad and Johannes Taucher and Renee Wilson and David Standaert and Carly Linder and Marne Baca",

note = "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.",

year = "2018",

month = dec,

doi = "10.1002/acn3.644",

language = "English",

volume = "5",

pages = "1460--1477",

journal = "Annals of Clinical and Translational Neurology",

issn = "2328-9503",

publisher = "John Wiley & Sons",

number = "12",

}

Marek, K, Chowdhury, S, Siderowf, A, Lasch, S, Coffey, CS, Caspell-Garcia, C, Simuni, T, Jennings, D, Tanner, CM, Trojanowski, JQ, Shaw, LM, Seibyl, J, Schuff, N, Singleton, A, Kieburtz, K, Toga, AW, Mollenhauer, B, Galasko, D, Chahine, LM, Weintraub, D, Foroud, T, Tosun-Turgut, D, Poston, K, Arnedo, V, Frasier, M, Sherer, T & Parkinson's Progression Markers Initiative 2018, 'The Parkinson's progression markers initiative (PPMI): establishing a PD biomarker cohort', Annals of Clinical and Translational Neurology, vol. 5, no. 12, pp. 1460-1477. https://doi.org/10.1002/acn3.644

TY - JOUR

T1 - The Parkinson's progression markers initiative (PPMI)

T2 - establishing a PD biomarker cohort

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 - Parkinson's Progression Markers Initiative

AU - Bressman, Susan

AU - Merchant, Kalpana 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 Elise

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

AU - Jankovic, Joseph

AU - Stern, Matthew

AU - Hu, Shu-Ching

AU - Todd, Gretchen

AU - Saunders-Pullman, Rachel

AU - Richard, Irene

AU - Saint-Hilaire, Marie H.

AU - Seppi, Klaus

AU - Shill, Holly

AU - Fernandez, Hubert

AU - Trenkwalder, Claudia

AU - Oertel, Wolfgang

AU - Berg, Daniela

AU - Brockman, Kathrin

AU - Wurster, Isabel

AU - Rosenthal, Liana

AU - Tai, Yen

AU - Pavese, Nicola

AU - Barone, Paolo

AU - Isaacson, Stuart

AU - Espay, Alberto

AU - Rowe, Dominic

AU - Brandabur, Melanie

AU - Tetrud, James

AU - Liang, Grace

AU - Iranzo, Alex

AU - Tolosa, Eduardo

AU - Marder, Karen

AU - de Arriba Sanchez, Maria

AU - Stefanis, Leonidis

AU - Marti, Maria Jose

AU - Martinez, Javier Ruiz

AU - Corvol, Jean-Christophe

AU - Assly, Jan O.

AU - Brillman, Salima

AU - Giladi, Nir

AU - Smejdir, Debra

AU - Pelaggi, Julia

AU - Kausar, Farah

AU - Rees, Linda

AU - Sommerfield, Barbara

AU - Cresswell, Madeline

AU - Blair, Courtney

AU - Williams, Karen

AU - Zimmerman, Grace

AU - Guthrie, Stephanie

AU - Rawlins, Ashlee

AU - Donharl, Leigh

AU - Hunter, Christine

AU - Tran, Baochan

AU - Darin, Abigail

AU - Venkov, Heli

AU - Thomas, Cathi-Ann

AU - James, Raymond

AU - Heim, Beatrice

AU - Deritis, Paul

AU - Sprenger, Fabienne

AU - Raymond, Deborah

AU - Willeke, Diana

AU - Obradov, Zoran

AU - Mule, Jennifer

AU - Monahan, Nancy

AU - Gauss, Katharina

AU - Fontaine, Deborah

AU - Szpak, Daniel

AU - McCoy, Arita

AU - Dunlop, Becky

AU - Payne, Laura Marie

AU - Ainscough, Susan

AU - Carvajal, Lisbeth

AU - Silverstein, Rebecca

AU - Espay, Kristy

AU - Ranola, Madelaine

AU - Rezola, Elisabet Mondragon

AU - Santana, Helen Mejia

AU - Stamelou, Maria

AU - Garrido, Alicia

AU - Carvalho, Stephanie

AU - Kristiansen, Anne Grete

AU - Specketer, Krista

AU - Mirlman, Anat

AU - Facheris, Maurizio

AU - Soares, Holly

AU - Mintun, Mark A.

AU - Cedarbaum, Jesse

AU - Taylor, Peggy

AU - Slieker, Lawrence

AU - McBride, Brian

AU - Watson, Colin

AU - Montagut, Etienne

AU - Sheikh, Zulfiqar Haider

AU - Bingol, Baris

AU - Forrat, Remi

AU - Sardi, Pablo

AU - Fischer, Tanya

AU - Reith, Alastair D.

AU - Egebjerg, Jan

AU - Larsen, Lone Frydelund

AU - Breysse, Nathalie

AU - Meulien, Didier

AU - Saba, Barbara

AU - Kiyasova, Vera

AU - Min, Chris

AU - McAvoy, Thomas

AU - Umek, Robert

AU - Iredale, Philip

AU - Edgerton, Jeremy

AU - De Santi, Susan

AU - Czech, Christian

AU - Boess, Frank

AU - Sevigny, Jeffrey

AU - Kremer, Thomas

AU - Grachev, Igor

AU - Avbersek, Andreja

AU - Muglia, Pierandrea

AU - Stewart, Alexandra

AU - Prashad, Rene

AU - Taucher, Johannes

AU - Wilson, Renee

AU - Standaert, David

AU - Linder, Carly

AU - Baca, Marne

N1 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85055893238&partnerID=8YFLogxK

U2 - 10.1002/acn3.644

DO - 10.1002/acn3.644

M3 - Article

C2 - 30564614

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 -

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

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