npj Parkinson's Disease (Sep 2024)
Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts
- Tien Dam,
- Gennaro Pagano,
- Michael C. Brumm,
- Caroline Gochanour,
- Kathleen L. Poston,
- Daniel Weintraub,
- Lana M. Chahine,
- Christopher Coffey,
- Caroline M. Tanner,
- Catherine M. Kopil,
- Yuge Xiao,
- Sohini Chowdhury,
- Luis Concha-Marambio,
- Peter DiBiaso,
- Tatiana Foroud,
- Mark Frasier,
- Danna Jennings,
- Karl Kieburtz,
- Kalpana Merchant,
- Brit Mollenhauer,
- Thomas J. Montine,
- Kelly Nudelman,
- John Seibyl,
- Todd Sherer,
- Andrew Singleton,
- Diane Stephenson,
- Matthew Stern,
- Claudio Soto,
- Eduardo Tolosa,
- Andrew Siderowf,
- Billy Dunn,
- Tanya Simuni,
- Kenneth Marek,
- the Parkinson’s Progression Markers Initiative
Affiliations
- Tien Dam
- Biogen
- Gennaro Pagano
- F. Hoffmann-La Roche Ltd.
- Michael C. Brumm
- Department of Biostatistics, College of Public Health, University of Iowa
- Caroline Gochanour
- Department of Biostatistics, College of Public Health, University of Iowa
- Kathleen L. Poston
- Department of Neurology, Stanford University School of Medicine
- Daniel Weintraub
- University of Pennsylvania and the Parkinson’s Disease and Mental Illness Research, Education and Clinical Centers (PADRECC and MIRECC), Philadelphia Veterans Affairs Medical Center
- Lana M. Chahine
- Department of Neurology, University of Pittsburgh
- Christopher Coffey
- Department of Biostatistics, College of Public Health, University of Iowa
- Caroline M. Tanner
- Department of Neurology, Movement Disorders and Neuromodulation Center, Weill Institute for Neuroscience, University of California
- Catherine M. Kopil
- The Michael J. Fox Foundation for Parkinson’s Research
- Yuge Xiao
- The Michael J. Fox Foundation for Parkinson’s Research
- Sohini Chowdhury
- The Michael J. Fox Foundation for Parkinson’s Research
- Luis Concha-Marambio
- Amprion Inc.
- Peter DiBiaso
- Patient Council, The Michael J. Fox Foundation for Parkinson’s Research
- Tatiana Foroud
- Department of Medical and Molecular Genetics, Indiana University
- Mark Frasier
- The Michael J. Fox Foundation for Parkinson’s Research
- Danna Jennings
- Denali Therapeutics Inc.
- Karl Kieburtz
- Department of Neurology, University of Rochester Medical Center
- Kalpana Merchant
- Department of Neurology, Northwestern University Feinberg School of Medicine
- Brit Mollenhauer
- Department of Neurology, University Medical Center Göttingen and Paracelsus-Elena-Klinik
- Thomas J. Montine
- Department of Pathology, Stanford University School of Medicine
- Kelly Nudelman
- Department of Medical and Molecular Genetics, Indiana University
- John Seibyl
- Institute for Neurodegenerative Disorders
- Todd Sherer
- The Michael J. Fox Foundation for Parkinson’s Research
- Andrew Singleton
- National Institute on Aging, National Institutes of Health
- Diane Stephenson
- Critical Path for Parkinson’s, Critical Path Institute
- Matthew Stern
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania
- Claudio Soto
- Amprion Inc.
- Eduardo Tolosa
- Parkinson’s Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, IDIBAPS, Universitat de Barcelona
- Andrew Siderowf
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania
- Billy Dunn
- The Michael J. Fox Foundation for Parkinson’s Research
- Tanya Simuni
- Department of Neurology, Northwestern University Feinberg School of Medicine
- Kenneth Marek
- Institute for Neurodegenerative Disorders
- the Parkinson’s Progression Markers Initiative
- DOI
- https://doi.org/10.1038/s41531-024-00789-w
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 12
Abstract
Abstract The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson’s disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1741 participants had SAA data and of these 1030 (59%) were S+ consistent with NSD. Among sporadic PD, 683/736 (93%) were NSD, and the distribution for Stages 2B, 3, and 4 was 25%, 63%, and 9%, respectively. Median (95% CI) time to developing a clinically meaningful outcome was 8.3 (6.2, 10.1), 5.9 (4.1, 6.0), and 2.4 (1.0, 4.0) years for baseline stage 2B, 3, and 4, respectively. We propose pilot biologic and clinical anchors for NSD-ISS. Our results highlight the baseline heterogeneity of individuals currently defined as early PD. Baseline stage predicts time to progression to clinically meaningful milestones. Further research on validation of the anchors in longitudinal cohorts is necessary.
