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; Dilinuer Wubuli; Karen Williams; Diana Willeke; Catherine Wandell; Alejandra Valenzuela; Bobbie Stubbeman; Angela Stovall; Barbara Sommerfeld; Elisabeth Sittig; Anisha Singh; Cristina Simonet; Clarissa Sanchez; Stephanie Roman; Janelle Rodriguez; Kyle Rizer; Kori Ribb; Taina M. Marques; Statistics Core; Imaging Core; Screening Core; Data Management Core; Strategy and Technical Operations; Site Management Core; Study Cores, Committees, and Related Studies; Michael J. Fox Foundation (Sponsor); Steering Committee; Executive Steering Committee; Project Management Core; the Parkinson’s Progression Markers Initiative; Coordinators; Site Investigators; PPMI Online; Found; Pathology Core; Genetics Core; Biologics Review Committee; Biorepository Core; Bioinformatics Core

doi:10.1038/s41531-024-00789-w

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 MollenhauerThomas 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, Dilinuer Wubuli, Karen Williams, Diana Willeke, Catherine Wandell, Alejandra Valenzuela, Bobbie Stubbeman, Angela Stovall, Barbara Sommerfeld, Elisabeth Sittig, Anisha Singh, Cristina Simonet, Clarissa Sanchez, Stephanie Roman, Janelle Rodriguez, Kyle Rizer, Kori Ribb, Taina M. Marques, Statistics Core, Imaging Core, Screening Core, Data Management Core, Strategy and Technical Operations, Site Management Core, Study Cores, Committees, and Related Studies, Michael J. Fox Foundation (Sponsor), Steering Committee, Executive Steering Committee, Project Management Core, the Parkinson’s Progression Markers Initiative, Coordinators, Site Investigators, PPMI Online, Found, Pathology Core, Genetics Core, Biologics Review Committee, Biorepository Core, Bioinformatics Core

^*Corresponding author for this work

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

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.

Original language	English
Article number	178
Pages (from-to)	178
Journal	npj Parkinson's Disease
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41531-024-00789-w
Publication status	Published - 27 Sept 2024
Externally published	Yes

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10.1038/s41531-024-00789-w

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Dam, T., Pagano, G., Brumm, M. C., Gochanour, C., Poston, K. L., Weintraub, D., Chahine, L. M., Coffey, C., Tanner, C. M., Kopil, C. M., Xiao, Y., Chowdhury, S., Concha-Marambio, L., DiBiaso, P., Foroud, T., Frasier, M., Jennings, D., Kieburtz, K., Merchant, K., ... Bioinformatics Core (2024). Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts. npj Parkinson's Disease, 10(1), 178. Article 178. https://doi.org/10.1038/s41531-024-00789-w

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title = "Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts",

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{\textquoteright}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.",

author = "Tien Dam and Gennaro Pagano and Brumm, {Michael C.} and Caroline Gochanour and Poston, {Kathleen L.} and Daniel Weintraub and Chahine, {Lana M.} and Christopher Coffey and Tanner, {Caroline M.} and Kopil, {Catherine M.} and Yuge Xiao and Sohini Chowdhury and Luis Concha-Marambio and Peter DiBiaso and Tatiana Foroud and Mark Frasier and Danna Jennings and Karl Kieburtz and Kalpana Merchant and Brit Mollenhauer and Montine, {Thomas J.} and Kelly Nudelman and John Seibyl and Todd Sherer and Andrew Singleton and Diane Stephenson and Matthew Stern and Claudio Soto and Eduardo Tolosa and Andrew Siderowf and Billy Dunn and Tanya Simuni and Kenneth Marek and Dilinuer Wubuli and Karen Williams and Diana Willeke and Catherine Wandell and Alejandra Valenzuela and Bobbie Stubbeman and Angela Stovall and Barbara Sommerfeld and Elisabeth Sittig and Anisha Singh and Cristina Simonet and Clarissa Sanchez and Stephanie Roman and Janelle Rodriguez and Kyle Rizer and Kori Ribb and Marques, {Taina M.} and {Statistics Core} and {Imaging Core} and {Screening Core} and {Data Management Core} and {Strategy and Technical Operations} and {Site Management Core} and {Study Cores, Committees, and Related Studies} and {Michael J. Fox Foundation (Sponsor)} and {Steering Committee} and {Executive Steering Committee} and {Project Management Core} and {the Parkinson{\textquoteright}s Progression Markers Initiative} and Coordinators and {Site Investigators} and {PPMI Online} and Found and {Pathology Core} and {Genetics Core} and {Biologics Review Committee} and {Biorepository Core} and {Bioinformatics Core}",

note = "{\textcopyright} 2024. The Author(s).",

year = "2024",

month = sep,

day = "27",

doi = "10.1038/s41531-024-00789-w",

language = "English",

volume = "10",

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journal = "npj Parkinson's Disease",

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Dam, T, Pagano, G, Brumm, MC, Gochanour, C, Poston, KL, Weintraub, D, Chahine, LM, Coffey, C, Tanner, CM, Kopil, CM, Xiao, Y, Chowdhury, S, Concha-Marambio, L, DiBiaso, P, Foroud, T, Frasier, M, Jennings, D, Kieburtz, K, Merchant, K, Mollenhauer, B, Montine, TJ, Nudelman, K, Seibyl, J, Sherer, T, Singleton, A, Stephenson, D, Stern, M, Soto, C, Tolosa, E, Siderowf, A, Dunn, B, Simuni, T, Marek, K, Wubuli, D, Williams, K, Willeke, D, Wandell, C, Valenzuela, A, Stubbeman, B, Stovall, A, Sommerfeld, B, Sittig, E, Singh, A, Simonet, C, Sanchez, C, Roman, S, Rodriguez, J, Rizer, K, Ribb, K, Marques, TM, Statistics Core, Imaging Core, Screening Core, Data Management Core, Strategy and Technical Operations, Site Management Core, Study Cores, Committees, and Related Studies, Michael J. Fox Foundation (Sponsor), Steering Committee, Executive Steering Committee, Project Management Core, the Parkinson’s Progression Markers Initiative, Coordinators, Site Investigators, PPMI Online, Found, Pathology Core, Genetics Core, Biologics Review Committee, Biorepository Core & Bioinformatics Core 2024, 'Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts', npj Parkinson's Disease, vol. 10, no. 1, 178, pp. 178. https://doi.org/10.1038/s41531-024-00789-w

TY - JOUR

T1 - Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts

AU - Dam, Tien

AU - Pagano, Gennaro

AU - Brumm, Michael C.

AU - Gochanour, Caroline

AU - Poston, Kathleen L.

AU - Weintraub, Daniel

AU - Chahine, Lana M.

AU - Coffey, Christopher

AU - Tanner, Caroline M.

AU - Kopil, Catherine M.

AU - Xiao, Yuge

AU - Chowdhury, Sohini

AU - Concha-Marambio, Luis

AU - DiBiaso, Peter

AU - Foroud, Tatiana

AU - Frasier, Mark

AU - Jennings, Danna

AU - Kieburtz, Karl

AU - Merchant, Kalpana

AU - Mollenhauer, Brit

AU - Montine, Thomas J.

AU - Nudelman, Kelly

AU - Seibyl, John

AU - Sherer, Todd

AU - Singleton, Andrew

AU - Stephenson, Diane

AU - Stern, Matthew

AU - Soto, Claudio

AU - Tolosa, Eduardo

AU - Siderowf, Andrew

AU - Dunn, Billy

AU - Simuni, Tanya

AU - Marek, Kenneth

AU - Wubuli, Dilinuer

AU - Williams, Karen

AU - Willeke, Diana

AU - Wandell, Catherine

AU - Valenzuela, Alejandra

AU - Stubbeman, Bobbie

AU - Stovall, Angela

AU - Sommerfeld, Barbara

AU - Sittig, Elisabeth

AU - Singh, Anisha

AU - Simonet, Cristina

AU - Sanchez, Clarissa

AU - Roman, Stephanie

AU - Rodriguez, Janelle

AU - Rizer, Kyle

AU - Ribb, Kori

AU - Marques, Taina M.

AU - Statistics Core

AU - Imaging Core

AU - Screening Core

AU - Data Management Core

AU - Strategy and Technical Operations

AU - Site Management Core

AU - Study Cores, Committees, and Related Studies

AU - Michael J. Fox Foundation (Sponsor)

AU - Steering Committee

AU - Executive Steering Committee

AU - Project Management Core

AU - the Parkinson’s Progression Markers Initiative

AU - Coordinators

AU - Site Investigators

AU - PPMI Online

AU - Found

AU - Pathology Core

AU - Genetics Core

AU - Biologics Review Committee

AU - Biorepository Core

AU - Bioinformatics Core

PY - 2024/9/27

Y1 - 2024/9/27

N2 - 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.

AB - 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.

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U2 - 10.1038/s41531-024-00789-w

DO - 10.1038/s41531-024-00789-w

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AN - SCOPUS:85205695610

SN - 2373-8057

VL - 10

SP - 178

JO - npj Parkinson's Disease

JF - npj Parkinson's Disease

IS - 1

M1 - 178

ER -

Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts

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