ArticlemedRxiv : the preprint server for health sciences2024
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 and 24 more
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In one paragraphArticle in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
34 authors.
Michael C BrummDepartment of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA.ORCID 0000-0002-3173-9989 Caroline GochanourDepartment of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA.ORCID 0009-0009-3263-8344 Kathleen L PostonDepartment of Neurology, Stanford University School of Medicine, Palo Alto, CA, USA.ORCID 0000-0003-3424-7143 Daniel WeintraubUniversity of Pennsylvania and the Parkinson's Disease and Mental Illness Research, Education and Clinical Centers (PADRECC and MIRECC), Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA.ORCID 0000-0003-0633-7168 Christopher CoffeyDepartment of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA.
Caroline M TannerMovement Disorders and Neuromodulation Center, Department of Neurology, Weill Institute for Neuroscience, University of California, San Francisco, CA, USA.ORCID 0000-0002-3775-5082 Peter DiBiasoPatient Council, The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.
Tatiana ForoudDepartment of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA.ORCID 0000-0002-5549-2212 Kalpana MerchantDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0003-1118-9403 Brit MollenhauerDepartment of Neurology, University Medical Center Göttingen and Paracelsus-Elena-Klinik, Kassel, Germany.ORCID 0000-0001-8437-3645 Kelly NudelmanDepartment of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA.ORCID 0000-0003-4040-1717 Diane StephensonCritical Path for Parkinson's, Critical Path Institute, Tucson, AZ, USA.
Matthew SternDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Eduardo TolosaParkinson'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, Barcelona, Spain.ORCID 0000-0002-3781-0854 Andrew SiderowfDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-1750-7698 Billy DunnSenior Advisor, The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.
Tanya SimuniDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0002-2361-6604 Parkinson’s Progression Markers Initiative
Funding
Stanford Alzheimer's Disease Research CenterAdmin Supp: Developing iPSC models for AD and PDP30AG066515 · NIA · STANFORD UNIVERSITY · PI Victor Henderson · 2020 to 2026
$29.0MUdall Center Director's meeting poster awardP50NS062684 · NINDS · UNIVERSITY OF WASHINGTON · PI MONTINE, THOMAS J · 2009 to 2020
$18.3MProject 4: Novel reagent development to enable molecular characterizationU19AG065156 · NIA · UNIVERSITY OF WASHINGTON · PI MONTINE, THOMAS J · 2020 to 2024
$15.9MThe impact of early Tau pathology on cognitive progression and neuropsychiatric symptoms in Parkinson's diseaseR01NS115114 · NINDS · STANFORD UNIVERSITY · PI ANDREASSON, KATRIN I., POSTON, KATHLEEN LOMBARD · 2019 to 2023
$4.2MAnalytical validation of a biochemical test for alpha-synuclein aggregates in biological fluids for the diagnosis of Parkinson's DiseaseU44NS111672 · NINDS · AMPRION, INC. · PI MACLEOD, KAREN · 2020 to 2022
$2.3MBasal Ganglia Modulation of Cognitive Systems in Parkinson's diseaseK23NS075097 · NINDS · STANFORD UNIVERSITY · PI POSTON, KATHLEEN LOMBARD · 2011 to 2015
$936kNIA NIH HHS P30 AG066515NIA NIH HHS U19 AG065156NINDS NIH HHS K23 NS075097NINDS NIH HHS P50 NS062684NINDS NIH HHS R01 NS115114NINDS NIH HHS U44 NS111672
6 · The paper itselfAbstract
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 1,741 participants had SAA data and of these 1,030 (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.
Indexed as
Biological definitionDementia with Lewy BodiesNeuronal Alpha-Synuclein DiseaseParkinson’s disease
Identifiers
PMID39314957
PMCPMC11419206
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LicenceCC BY
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