biostudies-literatureUnknown40(7)Simuni TMichael J. Fox Foundation for Parkinson's ResearchMichael J. Fox Foundation for Parkinson&apos;s Research<h4>Background</h4>Neuronal α-synuclein disease (NSD) is defined by the presence of an in vivo biomarker of neuronal alpha-synuclein (n-asyn) pathology. The NSD integrated staging system (NSD-ISS) for research describes progression across the disease continuum as stages 0 to 6.<h4>Objective</h4>The aim was to assess 5-year longitudinal change in NSD-ISS in early disease.<h4>Methods</h4>Analysis included a subset of participants from the Parkinson's Progression Markers Initiative (PPMI) enrolled before 2020 as Parkinson's disease (PD) patients, prodromal PD patients, or healthy controls (HC) who met NSD criteria. Staging was defined based on biomarkers of n-asyn and dopaminergic dysfunction in early stages, clinical features, and severity of functional impairment in stages 3 to 6. Stages weMovement disorders : official journal of the Movement Disorder Society1318-1330https://www.ebi.ac.uk/biostudies/studies/S-EPMC12273616biostudies-literatureNeuronal α-Synuclein Disease Stage Progression over 5 Years.PMC12273616Stephenson DTolosa EClark KValenzuela AWillson TFlagg EWilliams KRazzaque JGarrido ATanner CRuffrage LBressman SPoston KHu SCTosun-Turgut DO'Brien LJames RStandaert DSantana HMHobbick CEspay AKieburtz KPahwa RSingleton AMontine TDahodwala NO'Grady ABarone PKoros CNSD Working Group the Parkinson's Progression Markers InitiativeMule JMestre TRussell DHauser RShill HOnyinanya OGrummer MGochanour CWubuli DPoston KLHuntzinger CChahine LHeathers LHu MMarras CPagano GPavese NKrasowski YNair ARDeLano KRiley EFoster VKFrasier MOkubadejo NWeintraub DDam TKrueger RSantos NHammer JSchwarzschild MBruggemann NRamachandran AFerrari FLe DEshel MBrumm MCShaw LMantri SKirsch LChahine LMPennente LFernandez HShoulson IXiao YO'Shea SSchneider RSingh AChung IVidenovic APileggi MKlein CSchlett WSanchez CKopil CMTai YMerchant KFabrizio KBotting EAlcalay RRiboldi GRoman SPoewe WOjo OBrown EEgner IAntonopoulos GMcFarland NWandell CHerrera BMari ZMoukheiber EGalasko DCroitoru ITarakad AIsaacson SHilt EStubbeman BEcklund DRibb KMcMahon BAdler CAmara AGonzalez-Latapi PForoud TSeibyl JStovall ASiderowf AReddie SMarek KBressman BBSSommerfeld BMollenhauer BTrenkwalder CFactor SDobkin RMarti MJOertel WSaint-Hilaire MHCoffey CDunn BKopil KRowbotham HRodriguez JChowdhury SRizer KStefanis LSittig ELiu YMartinez JRSimonet CChou KBrumm MBrockmann KSimuni TRaymond DSherer THuff TNoyce AMosovsky SStanley CCaspell-Garcia CMarques TMAinscough SPerrotti RCasalin PShprecher DFullard MEberling JOgunleye ABlair CNg PEsha FKorell MHogarth PLew MKausar FKuhl MMWilleke DTanner CMPostuma RfalseNeuronal α-Synuclein Disease Stage Progression over 5 Years.<h4>Background</h4>Neuronal α-synuclein disease (NSD) is defined by the presence of an in vivo biomarker of neuronal alpha-synuclein (n-asyn) pathology. The NSD integrated staging system (NSD-ISS) for research describes progression across the disease continuum as stages 0 to 6.<h4>Objective</h4>The aim was to assess 5-year longitudinal change in NSD-ISS in early disease.<h4>Methods</h4>Analysis included a subset of participants from the Parkinson's Progression Markers Initiative (PPMI) enrolled before 2020 as Parkinson's disease (PD) patients, prodromal PD patients, or healthy controls (HC) who met NSD criteria. Staging was defined based on biomarkers of n-asyn and dopaminergic dysfunction in early stages, clinical features, and severity of functional impairment in stages 3 to 6. Stages we2025-01-01T00:00:00Z2025 Jul2026-07-15T08:57:46.258Z2025-08-27T03:06:59.852ZS-EPMC122736164030252710.1002/mds.30191