ACKNOWLEDGEMENTS
We wish to extend our gratitude to all data owners for their dedication to the principles of open science, demonstrated by their willingness to share their data.
The A4 Study is a secondary prevention trial in preclinical Alzheimer's disease, aiming to slow cognitive decline associated with brain amyloid accumulation in clinically normal older individuals. The A4 Study is funded by a public-private-philanthropic partnership, including funding from the National Institutes of Health-National Institute on Aging, Eli Lilly and Company, Alzheimer's Association, Accelerating Medicines Partnership, GHR Foundation, an anonymous foundation and additional private donors, with in-kind support from Avid and Cogstate. The companion observational Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study is funded by the Alzheimer's Association and GHR Foundation. The A4 and LEARN Studies are led by Dr. Reisa Sperling at Brigham and Women's Hospital, Harvard Medical School and Dr. Paul Aisen at the Alzheimer's Therapeutic Research Institute (ATRI), University of Southern California. The A4 and LEARN Studies are coordinated by ATRI at the University of Southern California, and the data are made available through the Laboratory for Neuro Imaging at the University of Southern California. The participants screening for the A4 Study provided permission to share their de-identified data in order to advance the quest to find a successful treatment for Alzheimer's disease. We would like to acknowledge the dedication of all the participants, the site personnel, and all of the partnership team members who continue to make the A4 and LEARN Studies possible. The complete A4 Study Team list is available on: a4study.org/a4-study-team.
Data collection and sharing of ABVIB was funded by the National Institutes on Aging (NIA) P01 AG12435.
Data collection and sharing of ARWIBO wthe as supported by the Italian Ministry of Health, under the following grant agreements: Ricerca Corrente IRCCS Fatebenefratelli, Linea di Ricerca 2; Progetto Finalizzato Strategico 2000-2001 “Archivio normativo italiano di morfometria cerebrale con risonanza magnetica (età 40+)”; Progetto Finalizzato Strategico 2000-2001 “Decadimento cognitivo lieve non dementigeno: stadio preclinico di malattia di Alzheimer e demenza vascolare. Caratterizzazione clinica, strumentale, genetica e neurobiologica e sviluppo di criteri diagnostici utilizzabili nella realtà nazionale,”; Progetto Finalizzata 2002 “Sviluppo di indicatori di danno cerebrovascolare clinicamente significativo alla risonanza magnetica strutturale”; Progetto Fondazione CARIPLO 2005-2007 “Geni di suscettibilità per gli endofenotipi associati a malattie psichiatriche e dementigene”; “Fitness and Solidarietà”; and anonymous donors. Data used in the preparation of this article were obtained from the Alzheimer's Disease Repository Without Borders (ARWiBo) (www.arwibo.it). The Principal Investigator of ARWIBO is Giovanni B.Frisoni, MD, University Hospitals and University of Geneva, Geneva, Switzerland, and IRCCS Fatebenefratelli, The National Centre for Alzheimer’s and Mental Diseases, Brescia, Italy. ARWIBO is the result of effort of many researchers of IRCCS Fatebenefratelli: G.Binetti, MD, Neurobiology; L.Bocchio-Chiavetto, PhD, Neuropharmacology; M.Cotelli, PhD, Neuropsychology Unit; C.Minussi, PhD, Neurophysiology; M.Gennarelli, PhD, Genetic Unit; R.Ghidoni, PhD, Proteomics Unit; D.Moretti, MD, and O.Zanetti, MD, Alzheimer’s Unit.
PharmaCog was funded through the European Community’s ‘Seventh Framework’ Programme (FP7/2007-2013) for an innovative scheme, the Innovative Medicines Initiative (IMI). IMI is a young and unique public-private partnership, founded in 2008 by the pharmaceutical industry (represented by the European Federation of Pharmaceutical Industries and Associations), EFPIA and the European Communities (represented by the European Commission).
J-ADNI was supported by the following grants: Translational Research Promotion Project from the New Energy and Industrial Technology Development Organization of Japan; Research on Dementia, Health Labor Sciences Research Grant; Life Science Database Integration Project of Japan Science and Technology Agency; Research Association of Biotechnology (contributed by Astellas Pharma Inc., Bristol-Myers Squibb, Daiichi-Sankyo, Eisai, Eli Lilly and Company, Merck-Banyu, Mitsubishi Tanabe Pharma, Pfizer Inc., Shionogi & Co., Ltd., Sumitomo Dainippon, and Takeda Pharmaceutical Company), Japan, and a grant from an anonymous Foundation.
Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. This research was also supported by NIH grants P30 AG010129 and K01 AG030514.
Data used in the preparation of this article were obtained on March, 2nd 2023 from the Parkinson’s Progression Markers Initiative (PPMI) database (www.ppmi-info.org/access-data-specimens/download-data), RRID:SCR_006431. For up-to-date information on the study, visit www.ppmi-info.org. Funding: PPMI – a public-private partnership – is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including 4D Pharma, Abbvie, AcureX, Allergan, Amathus Therapeutics, Aligning Science Across Parkinson's, AskBio, Avid Radiopharmaceuticals, BIAL, Biogen, Biohaven, BioLegend, BlueRock Therapeutics, Bristol-Myers Squibb, Calico Labs, Celgene, Cerevel Therapeutics, Coave Therapeutics, DaCapo Brainscience, Denali, Edmond J. Safra Foundation, Eli Lilly, Gain Therapeutics, GE HealthCare, Genentech, GSK, Golub Capital, Handl Therapeutics, Insitro, Janssen Neuroscience, Lundbeck, Merck, Meso Scale Discovery, Mission Therapeutics, Neurocrine Biosciences, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi, Servier, Sun Pharma Advanced Research Company, Takeda, Teva, UCB, Vanqua Bio, Verily, Voyager Therapeutics, the Weston Family Foundation and Yumanity Therapeutics. This analysis used data openly available from PPMI.
Data used in the preparation of this article were obtained from the Fox Investigation for New Discovery of Biomarkers (“BioFIND”) database (http://biofind.loni.usc.edu/). For up-to-date information on the study, visit www.michaeljfox.org/biofind. BioFIND is sponsored by The Michael J. Fox Foundation for Parkinson’s Research (MJFF) with support from the National Institute for Neurological Disorders and Stroke (NINDS).
Data used in preparation of this article were obtained from the MJFF-sponsored LRRK2 Cohort Consortium (LCC). For up-to-date information on the study, visit www.michaeljfox.org/lcc. The LRRK2 Cohort Consortium is coordinated and funded by The Michael J. Fox Foundation for Parkinson’s Research. The investigators within the LCC contributed to the design and implementation of the LCC and/or provided data and/or collected biospecimens, but did not necessarily participate in the analysis or writing of this report. The full list of LCC investigators can be found at www.michaeljfox.org/lccinvestigators.
Samples and associated clinical data were supplied by the Tracking Parkinson’s (PRoBaND) study, funded by Parkinson’s UK (Grant ref J-1101), a charity registered in England and Wales (2581970) and in Scotland (SC037554), with the support of the Comprehensive Local Research Network.
Data used in the preparation of this manuscript were obtained from the National Centre of Excellence in Research on Parkinson's Disease (NCER-PD). The National Centre of Excellence in Research on Parkinson's Disease (NCER-PD) is funded by the Luxembourg National Research Fund (FNR/NCER13/BM/11264123). We would like to thank all participants of the Luxembourg Parkinson’s Study for their important support of our research. Furthermore, we acknowledge the joint effort of the National Centre of Excellence in Research on Parkinson’s Disease (NCER-PD) Consortium members from the partner institutions Luxembourg Centre for Systems Biomedicine, Luxembourg Institute of Health, Centre Hospitalier de Luxembourg, and Laboratoire National de Santé generally contributing to the Luxembourg Parkinson’s Study as listed below:
Geeta ACHARYA2, Gloria AGUAYO2, Myriam ALEXANDRE2, Muhammad ALI1, Wim AMMERLANN2, Giuseppe ARENA1, Rudi BALLING1, Michele BASSIS1, Roxane BATUTU3, Katy BEAUMONT2, Regina BECKER1, Camille BELLORA2, Guy BERCHEM3, Daniela BERG11, Alexandre BISDORFF5, Ibrahim BOUSSAAD1, David BOUVIER4, Kathrin BROCKMANN11, Jessica CALMES2, Lorieza CASTILLO2, Gessica CONTESOTTO2, Nancy DE BREMAEKER3, Nico DIEDERICH3, Rene DONDELINGER5, Nancy E. RAMIA1, Daniela ESTEVES2, Jean-Yves FERRAND2, Katrin FRAUENKNECHT4, Manon GANTENBEIN2, Thomas GASSER11, Piotr GAWRON1, Soumyabrata GHOSH1, Marijus GIRAITIS2,3, Enrico GLAAB1, Martine GOERGEN3, Elisa GÓMEZ DE LOPE1, Jérôme GRAAS2, Mariella GRAZIANO16, Valentin GROUES1, Anne GRÜNEWALD1, Wei GU1, Gaël HAMMOT2, Anne-Marie HANFF2,19,20, Linda HANSEN1,3, Michael HENEKA1, Estelle HENRY2, Sylvia HERBRINK6, Sascha HERZINGER1, Michael HEYMANN2, Michele HU8, Alexander HUNDT2, Nadine JACOBY17, Jacek JAROSLAW LEBIODA1, Yohan JAROSZ1, Sonja JÓNSDÓTTIR2, Quentin KLOPFENSTEIN1, Jochen KLUCKEN1,2,3, Rejko KRÜGER1,2,3, Pauline LAMBERT2, Zied LANDOULSI1, Roseline LENTZ7, Inga LIEPELT11, Robert LISZKA14, Laura LONGHINO3, Victoria LORENTZ2, Paula Cristina LUPU2, Tainá M. MARQUES2, Clare MACKAY10, Walter MAETZLER15, Katrin MARCUS13, Guilherme MARQUES2, Patricia MARTINS CONDE1, Patrick MAY1, Deborah MCINTYRE2, Chouaib MEDIOUNI2, Francoise MEISCH1, Myriam MENSTER2, Maura MINELLI2, Michel MITTELBRONN1,2,4,19,21,22, Brit MOLLENHAUER12, Friedrich MÜHLSCHLEGEL4, Romain NATI3, Ulf NEHRBASS2, Sarah NICKELS1, Beatrice NICOLAI3, Jean-Paul NICOLAY18, Fozia NOOR2, Marek OSTASZEWSKI1, Clarissa P. C. GOMES1, Sinthuja PACHCHEK1, Claire PAULY1,3, Laure PAULY2,19, Lukas PAVELKA1,3, Magali PERQUIN2, Rosalina RAMOS LIMA2, Armin RAUSCHENBERGER1, Rajesh RAWAL1, Dheeraj REDDY BOBBILI1, Kirsten ROOMP1, Eduardo ROSALES2, Isabel ROSETY1, Estelle SANDT2, Stefano SAPIENZA1, Venkata SATAGOPAM1, Margaux SCHMITT2, Sabine SCHMITZ1, Reinhard SCHNEIDER1, Jens SCHWAMBORN1, Raquel SEVERINO2, Amir SHARIFY2, Ekaterina SOBOLEVA1, Kate SOKOLOWSKA2, Hermann THIEN2, Elodie THIRY3, Rebecca TING JIIN LOO1, Christophe TREFOIS1, Johanna TROUET2, Olena TSURKALENKO2, Michel VAILLANT2, Mesele VALENTI2, Gilles VAN CUTSEM1,3, Carlos VEGA1, Liliana VILAS BOAS3, Maharshi VYAS1, Richard WADE-MARTINS9, Paul WILMES1, Evi WOLLSCHEID-LENGELING1, Gelani ZELIMKHANOV3
1 Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
2 Luxembourg Institute of Health, Strassen, Luxembourg
3 Centre Hospitalier de Luxembourg, Strassen, Luxembourg
4 Laboratoire National de Santé, Dudelange, Luxembourg
5 Centre Hospitalier Emile Mayrisch, Esch-sur-Alzette, Luxembourg
6 Centre Hospitalier du Nord, Ettelbrück, Luxembourg
7 Parkinson Luxembourg Association, Leudelange, Luxembourg
8 Oxford Parkinson's Disease Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
9 Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK
10 Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, Department of Psychiatry, University of Oxford, Oxford, UK
11 Center of Neurology and Hertie Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University Hospital Tübingen, Germany
12 Paracelsus-Elena-Klinik, Kassel, Germany
13 Ruhr-University of Bochum, Bochum, Germany
14 Westpfalz-Klinikum GmbH, Kaiserslautern, Germany
15 Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany
16 Association of Physiotherapists in Parkinson's Disease Europe, Esch-sur-Alzette, Luxembourg
17 Private practice, Ettelbruck, Luxembourg
18 Private practice, Luxembourg, Luxembourg
19 Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
20 Department of Epidemiology, CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre+, Maastricht, the Netherlands
21 Luxembourg Center of Neuropathology, Dudelange, Luxembourg
22 Department of Life Sciences and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
AUTHOR CONTRIBUTIONS
MHA and MJ designed the project. YS, MHA, and MCA collected the datasets. MCA and YS curated the datasets. TA and MCA implemented the model and generated the results. HB assisted with model selection. TA, YS, MCA, HB, and MJ interpreted the results. YS and TA drafted the manuscript. MCA, HB, MJ, and MHA revised the manuscript. The authors read and approved the final manuscript.
DATA AVAILABILITY
We declare that the data utilized in this study are not owned by the authors, and therefore, cannot be shared due to data privacy considerations. For inquiries regarding access to the data, interested parties are advised to contact the original data owners directly.
CODE AVAILABILITY
The code is available at: https://github.com/SCAI-BIO/index as well as https://github.com/SCAI-BIO/tsnepad
CONFLICT OF INTERESTS STATEMENT
The authors declare no competing interests.
FUNDING
This work was supported by internal Fraunhofer funding for the collaboration between Charité Berlin and Fraunhofer. HB was supported by funding from the Research Foundation - Flanders (Fonds Wetenschappelijk Onderzoek, FWO) grant 1154623N.
CONSENT STATEMENT
Consent was not required as no human subject information was utilized in this study.