Acknowledgements
Study Supported by:
PPMI – a public-private partnership – is funded by the Michael J. Fox Foundation for Parkinson’s Research funding partners 4D Pharma, Abbvie, Acurex Therapeutics, Allergan, Amathus Therapeutics, ASAP, Avid Radiopharmaceuticals, Bial Biotech, Biogen, BioLegend, Bristol-Myers Squibb, Calico, Celgene, Dacapo Brain Science, Denali, The Edmond J. Safra Foundaiton, GE Healthcare, Genentech, GlaxoSmithKline, Golub Capital, Handl Therapeutics, Insitro, Janssen Neuroscience, Lilly, Lundbeck, Merck, Meso Scale Discovery, Neurocrine Biosciences, Pfizer, Piramal, Prevail, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, and Voyager Therapeutics.”
Data used in the preparation of this article were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database (www.ppmi-info.org/data). For up-to-date information on the study, visit www.ppmi-info.org.
*Parkinson’s Progression Marker Initiative Authors
Executive Steering Committee:
Kenneth Marek, MD1 (Principal Investigator); Andrew Siderowf, MD, MSCE12 (Leadership Core, Site Investigator); Brit Mollenhauer, MD8 (Bioanalytics Core, co-PI; Site Investigator); Caroline Tanner, MD, PhD9 (co-PI); Dan Weintraub, MD12, Douglas Galasko, MD27 (Bioanalytics Core, co-PI; Site Investigator); Lana Chahine, MD67; Tanya Simuni, MD3 (Leadership Core, Site Investigator); Christopher Coffey, PhD4 (Statistics Core, PI); Kalpana Merchant, PhD68; Kathleen Poston, MD65 (Imaging Core); Roseanne Dobkin, PhD70, Tatiana Foroud, PhD15 (Biorepository Core, PI)
Steering Committee:
Duygu Tosun-Turgut, PhD9 (DTI Analysis Core, PI); Karl Kieburtz, MD, MPH5; Werner Poewe, MD7 (Site Investigator); Susan Bressman, MD14 (Site Investigator); Giulia Malferrari11 (Biorepository Core); Raymond James, RN22 (Site Coordinator); Ekemini Riley, PhD69; John Seibyl, MD1 (Imaging Core, PI); Leslie Shaw, PhD12; David Standaert, MD, PhD18; Sneha Mantri; Nabila Dahodwala, MD12; Michael Schwarzschild74; Connie Marras72; Hubert Fernandez, MD25, Ethan Brown, MD9, Chelsea Caspell4; Paola Casalin; Ira Shoulson; Helen Rowbotham; Madeleine Schloetter; Claudia Trenkwalder
Michael J. Fox Foundation (Sponsor): Todd Sherer, PhD; Sohini Chowdhury; Mark Frasier, PhD; Jamie Eberling, PhD; Samantha J. Hutten, PhD; Katie Kopil; Alyssa O’Grady
Study Cores:
Leadership Core: Kenneth Marek, MD1
Project Management Core: Emily Flagg1
Site Management Core: Bridget McMahon1
Imaging Core: John Seibyl, MD1
Biorepository Core: Tatiana Foroud, PhD15; Paola Casalin11; Giulia Malferrari11; Mali Gani Weisz61; Avi Orr-Urtreger, MD, PhD61
Statistics Core: Christopher Coffey, PhD4; Chelsea Caspell4; Janel Fedler, PhD4; Michael Brumm, MS4; David Erick LaFontant, MS4
Bioinformatics Core: Arthur Toga, PhD10; Karen Crawford10
Genetics Core: Andrew Singleton, PhD13
Pathology Core: Tatiana Foroud, PhD15; Thomas Montine, MD, PhD65
Site Investigators:
Ruth Schneider, MD23; Kelvin Chou, MD71; David Russell, MD, PhD1; Stewart Factor, DO16; Penelope Hogarth, MD17; Robert Hauser, MD, MBA19; Nabila Dahodwala, MD, MSc12; Marie H Saint-Hilaire, MD, FRCPC, FAAN22; David Shprecher, DO24; Hubert Fernandez, MD25; Kathrin Brockmann, MD26; Yen Tai, MD, PhD29; Paolo Barone, MD, PhD30; Stuart Isaacson, MD31; Alberto Espay, MD, MSc, FAAN, FANA32; Maria Jose Martí, MD, PhD34; Eduardo Tolosa MD, PhD34; Shu-Ching Hu, MD, PhD21; Douglas Galasko, MD27; Emile Moukheiber, MD28; Jean-Christophe Corvol, MD39; Nir Giladi, MD61; Javier Ruiz Martinez, MD, PhD60; Jan O. Aasly, MD62; Leonidas Stefanis, MD, PhD63; Karen Marder, MD MPH64 ; Arjun Tarakad, MD20; Connie Marras, MD, PhD, FRCP(C)72; Tiago Mestre, MD, PhD73; Aleksandar Videnovic, MD, MSc74; Rajesh Pahwa, MD75; Mark Lew, MD76; Holly Shill, MD77; Amy Amara, MD, PhD18; Charles Adler, MD, PhD78; Caroline Tanner, MD, PhD9; Susan Bressman, MD14; Tanya Simuni, MD3; Maureen Leehey, MD79; Giulietta Riboldi, MD80; Nikolaus McFarland, MD, PhD, FAAN81; Lana Chahine, MD67; Ron Postuma, MD, FRCPC82; Brit Mollenhauer, MD8; Werner Poewe, MD7; Zoltan Mari, MD83; Nicola Pavese, MD, PhD84; Michele Hu, MD, PhD85; Norbert Brüggemann, MD86; Christine Klein, MD, FEAN86; Bastiaan Bloem, MD, PhD87
Coordinators:
Anisha Singh, BS23; Angela Stovall, BS71; Julie Festa, BA1; Lianne Ramia, BS1; Katrina Wakeman, BS17; Karen Williams, BA, CCRP3; Courtney Blair, MA18; Krista Specketer, BS21; Diana Willeke8; Jennifer Mule, BS25; Ella Hilt26; Shawnees Peacock, BS27; Kori Ribb, RN, BSN, CNRN28; Susan Ainscough, BA30; Lisbeth Pennente, BA31; Julia Brown, BS32; Christina Gruenwald, BS, CCRP32; Barbara Sommerfeld MSN, RN, CNRN16; Farah Kausar, PhD9; Alicia Garrido, MD34; Deborah Raymond, MS, CGC14; Ioana Croitoru60; Anne Grete Kristiansen62; Helen Mejia Santana, MA64; Anjana Singh, BS20; Danica Nogo, BS72; Shawna Reddie, BA73; Samantha Murphy, BS74; Lauren O’Brien75; Ashwini Ramachandran, MSc12; Fnu Madhuri, MS19; Daniel Freire, MS76; Farah Ismail, MBChB77; Raymond James, BS, RN22; Tom Osgood, BA, CCRP78; Heidi Friedeck, BS3; Jenny Frisendahl, BS79; Ying Liu, MD79; Caitlin Romano, BA80; Kelly Clark24; Kyle Rizer, BA81; Stephanie Carvalho39; Sherri Mosovsky, MPH67; Farah Sulaiman, MPH82; Dora Valent, MS7; Raquel Lopes, BSN, MS29; Michelle Torreliza, AS83; Shira Paz, BS61; Victoria Kate Foster84; Madita Grümmer86; Myrthe Burgler, MA87; Sabine van Zundert, MS87; Christos Koros, MD, PhD63; Jamil Razzaque, MS85
Partners Scientific Advisory Board (Acknowledgement)
1 Institute for Neurodegenerative Disorders, New Haven, CT
3 Northwestern University, Chicago, IL
4 University of Iowa, Iowa City, IA
6 The Michael J. Fox Foundation for Parkinson’s Research, New York, NY
7 Innsbruck Medical University, Innsbruck, Austria
8 Paracelsus-Elena Klinik, Kassel, Germany
9 University of California, San Francisco, CA
10 Laboratory of Neuroimaging (LONI), University of Southern California
11 BioRep, Milan, Italy
12 University of Pennsylvania, Philadelphia, PA
13 National Institute on Aging, NIH, Bethesda, MD
14 Mount Sinai Beth Israel, New York, NY
15 Indiana University, Indianapolis, IN
16 Emory University of Medicine, Atlanta, GA
17 Oregon Health and Science University, Portland, OR
18 University of Alabama at Birmingham, Birmingham, AL
19 University of South Florida, Tampa, FL
20 Baylor College of Medicine, Houston, TX
21 University of Washington, Seattle, WA
22 Boston University, Boston, MA
23 University of Rochester, Rochester, NY
24 Banner Research Institute, Sun City, AZ
25 Cleveland Clinic, Cleveland, OH
26 University of Tuebingen, Tuebingen, Germany
27 University of California, San Diego, CA
28 Johns Hopkins University, Baltimore, MD
29 Imperial College of London, London, UK
30 University of Salerno, Salerno, Italy
31 Parkinson’s Disease and Movement Disorders Center, Boca Raton, FL
32 University of Cincinnati, Cincinnati, OH
34 Hospital Clinic of Barcelona, Barcelona, Spain
35 Pfizer, Inc., Groton, CT
36 Biogen, Cambridge, MA
37 GE Healthcare, Princeton, NJ
38 AbbVie, Abbot Park, IL
39 University Hospitals Pitié Salpêtrière, Paris, France
40 F.Hoffmann La-Roche, Basel, Switzerland
41 Merck & Co., North Wales, PA
42 Genentech, Inc., South San Francisco, CA
43 GlaxoSmithKline, Stevenage, United Kingdom
44 BioLegend, San Diego, CA
45 Lundbeck, Copenhagen, Denmark
46 Avid Radiopharmaceuticals, Philadelphia , PA
47 UCB Pharma S.A., Brussels, Belgium
48 Meso Scale Discovery
49 Piramal Life Sciences, Berlin, Germany
50 Servier
51 Allergan, Dublin, Ireland
52 Celgene, Summit, NJ
53 Denali Therapeutics, South San Francisco, CA
54 Eli Lilly and Company, Indianapolis, IN
55 Sanofi, Paris, France
56 Prevail Therapeutics, New York, NY
57 Takeda Pharmaceutical Company, Tokyo, Japan
58 Verily, South San Francisco, CA
59 Voyager Therapeutics, Cambridge, MA
60 Hospital Universitario Donostia, San Sebastian, Spain
61 Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
62 St. Olav’s University Hospital, Trondheim, Norway
63 National and Kapodistrian University of Athens, Athens, Greece
64 Columbia University Irving Medical Center, New York, NY
65 Stanford University, Stanford, CA
67 University of Pittsburgh, Pittsburgh, PA
68 Northwestern University Feinberg School of Medicine, Chicago, IL
69 Center for Strategy Philanthropy at Milken Institute, Washington D.C.
70 University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey
71 University of Michigan, Ann Arbor, MI
72 Toronto Western Hospital, Toronto, Canada
73 The Ottawa Hospital, Ottawa, Canada
74 Massachusetts General Hospital, Boston, MA
75 University of Kansas Medical Center, Kansas City, KS
76 University of Southern California, Los Angeles, CA
77 Barrow Neurological Institute, Phoenix, AZ
78 Mayo Clinic Arizona, Scottsdale, AZ
79 University of Colorado, Aurora, CO
80 NYU Langone Medical Center, New York, NY
81 University of Florida, Gainesville, FL
82 Montreal Neurological Institute and Hospital/McGill, Montreal, QC, Canada
83 Cleveland Clinic-Las Vegas Lou Ruvo Center for Brain Health, Las Vegas, NV
84 Clinical Ageing Research Unit, Newcastle, UK
85 John Radcliffe Hospital Oxford and Oxford University, Oxford, UK
86 Universität Lübeck, Luebeck, Germany
87 Radboud University, Nijmegen, Netherlands
Competing Interests Statement:
Tanya Simuni, MD
has served as a consultant for 4D Pharma, Acadia, AcureX, AskBio, Amneal, Blue Rock Therapeutics, Caraway Therapeutics, Critical Path for Parkinson's Consortium (CPP), Denali, Michael J Fox Foundation, Neuroderm, Sanofi, Sinopia, Sunovion, Roche, Takeda, UCB, Vanqua Bio and Voyager. Dr. Simuni served on the ad board for Acadia, AcureX, AskBio, Amneal, Denali, Sunovion, Roche. Dr. Simuni has served as a member of the scientific advisory board of 4D Pharma, Neuroderm, Sanofi and UCB. Dr. Simuni has received research funding from Amneal, Biogen, Roche, Neuroderm, Sanofi, Prevail and UCB and an investigator for NINDS, MJFF, Parkinson’s Foundation.
Michael C. Brumm, MS reports no disclosures.
Hyunkeun Ryan Cho, PhD reports no disclosures.
Chelsea Caspell-Garcia, MS reports no disclosures.
Christopher S. Coffey, PhD receives funding from NINDS, NHLBI, and the Michael J. Fox Foundation. He is also a paid consultant to MJFF.
Andrew Siderowf, MD has been a consultant to the following companies in the past year: Biogen, Merck, Denali, Wave Life Sciences and Prilenia Therapeutics. He has received grant funding from the Michael J. Fox Foundation and NINDS.
Tatiana Foroud, PhD receives funding from the National Institutes of Health (NIH), The Michael J. Fox Foundation, the US Department of Defense.
Kelly Nudelman, PhD receives funding from the National Institutes of Health (NIH), the Michael J. Fox Foundation, the National Collegiate Athletic Association, the United States Department of Defense, the United States Army Medical Research Acquisition Activity, the National Alzheimer’s Coordinating Center, the Indiana State Department of Health, the Lilly Endowment Incorporated, and Biohaven Pharmaceuticals, Inc.
Brit Mollenhauer, MD is employed by Parcacelsus Kliniken Germany and the University medical center Goettingen; BM has received independent research grants from TEVA-Pharma, Desitin, Boehringer Ingelheim, GE Healthcare and honoraria for consultancy from Bayer Schering Pharma AG, Roche, AbbVie, TEVA-Pharma, Biogen and for presentations from GlaxoSmithKline, Orion Pharma, TEVA-Pharma and travel costs from TEVA-Pharma. BM is member of the executive steering committee of the Parkinson Progression Marker Initiative and the Systemic Synuclein Sampling Study of the Michael J. Fox Foundation for Parkinson’s Research and has received grants from the BMBF, EU, Parkinson Fonds Deutschland, Deutsche Parkinson Vereinigung, Michael J. Fox Foundation for Parkinson’s Research, Stifterverband für die deutsche Wissenschaft, and has scientific collaborations with Roche, Bristol Myers Squibb, Ely Lilly, Covance and Biogen.
Caroline M. Tanner, MD, PhD is an employee of the San Francisco Veterans Affairs Medical Center and the University of California – San Francisco. She receives grants from the Michael J. Fox Foundation, the Parkinson’s Foundation, the Department of Defense, BioElectron, Roche/Genentech, Biogen Idec and the National Institutes of Health, compensation for serving on Data Monitoring Committees from Biotie Therapeutics, Voyager Therapeutics and Intec Pharma and personal fees for consulting from Neurocrine Biosciences, Adamas Therapeutics, Biogen Idec, 23andMe, Alexza, Grey Matter and CNS Ratings.
Lana M. Chahine, MD receives research support from the Michael J. Fox Foundation, UPMC Competitive Medical Research Fund, and University of Pittsburgh, support as site investigator for a study sponsored by Biogen, receives research support from the National Institutes of Health, receives consulting fees from Grey Matter Technologies, receives royalties from Elsevier (for authorship), and receives royalties from Wolters Kluwel (for authorship).
Roy Alcalay, MD MS, receives research support from the NIH, DoD, Parkinson’s Foundation, MJFF. He received consultation fees from Avrobio, Caraway, Merck, GSK, Ono Therapeutics, Sanofi and Takeda.
Hirotaka Iwaki, MD, PhD is a consultant employed by Data Tecnica International, whose participation in this is part of a consulting agreement between the US National Institutes of Health and said company.
Todd Sherer, PhD is employed by The Michael J. Fox Foundation.
Kenneth Marek is a consultant for MJFox Foundation, GE Healthcare, Biogen, Prothena, Roche, Neuropore, US Worldmeds, Proclara, Oxford Biomedica, Prevail, UCB, Neuraly, Lysosomal Therapetic, Inc, Neuroderm, Denali, Takeda W81XWH-06-1-0678 Establishing an 'at risk' cohort for Parkinson Disease Neuroprevention using olfactory testing and DAT imaging, DOD, Investigator 10/1/06 – 09/30/19; Parkinson Progression Marker Initiative (PPMI), Michael J. Fox Foundation, Principal Investigator; DAT imaging in LRRK2 family members, the Michael J. Fox Foundation, Principal Investigator 1/15/10 – 1/14/23. Ownership in Invicro, LLC
Authors contribution
Authors: Tanya Simuni Kalpana Merchant, Michael Brumm, Hyunkeun Cho, Chelsea Caspell-Garcia, Chris Coffey, Lana Chahine, Roy Alcalay, Kelly Nudelman, Tatiana Foroud, Brit Mollenhauer, Andrew Siderowf, Caroline Tanner, Hirotaka Iwaki, Todd Sherer, and Ken Marek
All authors contributed extensively to the work presented in this paper.
TS, KM, MB designed the analysis plan. MB, HC, CCG, CC assembled input data, wrote code, ran the model, and analyses output data. TS wrote the draft manuscript, all authors contributed to data analysis and critical review and revisions of the manuscript
Data Availability Statement ( added on page 7 )
PPMI is an open access dataset. Data used in the preparation of this manuscript were obtained from the PPMI database (www.ppmi-info.org/data). Study protocol and manuals are available at www.ppmi-info.org/study-design. The data used for this paper were downloaded June 30, 2020