| Title: |
Diagnostic and prognostic value of α-synuclein seed amplification assay kinetic measures in Parkinson's disease: a longitudinal cohort study |
| Authors: |
Orru C. D.; Vaughan D. P.; Vijiaratnam N.; Real R.; Martinez-Carrasco A.; Fumi R.; Jensen M. T.; Hodgson M.; Girges C.; Gil-Martinez A. -L.; Stafford E. J.; Wu L.; Lerche S.; Wurster I.; Groveman B. R.; Hughson A. G.; Ansorge O.; Quaegebeur A.; Allinson K. S. J.; Warner T. T.; Jaunmuktane Z.; Misbahuddin A.; Leigh P. N.; Ghosh B. C. P.; Bhatia K. P.; Church A.; Kobylecki C.; Hu M. T. M.; Rowe J. B.; Parchi P.; Brockmann K.; Foltynie T.; Morris H. R.; Caughey B.; Jabbari E. |
| Contributors: |
Orru, C. D.; Vaughan, D. P.; Vijiaratnam, N.; Real, R.; Martinez-Carrasco, A.; Fumi, R.; Jensen, M. T.; Hodgson, M.; Girges, C.; Gil-Martinez, A. -L.; Stafford, E. J.; Wu, L.; Lerche, S.; Wurster, I.; Groveman, B. R.; Hughson, A. G.; Ansorge, O.; Quaegebeur, A.; Allinson, K. S. J.; Warner, T. T.; Jaunmuktane, Z.; Misbahuddin, A.; Leigh, P. N.; Ghosh, B. C. P.; Bhatia, K. P.; Church, A.; Kobylecki, C.; Hu, M. T. M.; Rowe, J. B.; Parchi, P.; Brockmann, K.; Foltynie, T.; Morris, H. R.; Caughey, B.; Jabbari, E. |
| Publication Year: |
2025 |
| Collection: |
IRIS Università degli Studi di Bologna (CRIS - Current Research Information System) |
| Subject Terms: |
synuclein; seed amplification assay; RT-QuIC; LBD; Parkinson; prognosis; cognitive decline |
| Description: |
Background: α-synuclein seed amplification assay (SAA) positivity has been proposed as a diagnostic biomarker for Parkinson's disease. However, studies of the prognostic value of this biomarker have been limited to small, single-centre studies over short follow-up periods. We aimed to assess the diagnostic and prognostic value of quantitative CSF α-synuclein SAA kinetic measures in Parkinson's disease. Methods: In this longitudinal cohort study, we collected and analysed data from participants with Parkinson's disease, progressive supranuclear palsy, and healthy controls enrolled in three cohorts: the UK parkinsonism cohort, the Parkinson's Progression Markers Initiative (PPMI) international observational study, and the Tübingen Parkinson's disease cohort. Baseline CSF α-synuclein SAA data and longitudinal clinical data were collected between Jan 1, 2005, and Nov 1, 2023. The following seeding kinetic measures were calculated from the α-synuclein SAA curve for each SAA-positive sample: time to threshold (TTT) for a positive SAA result; maximum Thioflavin T fluorescence during the reaction time (MaxThT); and area under the fluorescence curve during the reaction time (AUC). We compared seeding kinetic measures between sporadic Parkinson's disease and progressive supranuclear palsy, and between sporadic Parkinson's disease and monogenic Parkinson's disease. We used time-to-event analyses to assess the ability of α-synuclein SAA kinetic measures to predict an unfavourable outcome in Parkinson's disease, adjusting for sex, age, and disease duration at SAA testing. Findings: We analysed data from 1631 participants: newly generated data from the UK parkinsonism cohort (Parkinson's disease, n=66; progressive supranuclear palsy, n=52; controls, n=9) and previously generated data from the PPMI (Parkinson's disease, n=1036; controls, n=239) and Tübingen (Parkinson's disease, n=229) cohorts. In the UK parkinsonism cohort, α-synuclein SAA was positive in 63 (96%) of 66 Parkinson's disease samples and eight (15%) of 52 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
STAMPA |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/40541208; info:eu-repo/semantics/altIdentifier/wos/WOS:001518187000004; volume:24; issue:7; firstpage:580; lastpage:590; numberofpages:11; journal:LANCET NEUROLOGY; https://hdl.handle.net/11585/1039095; https://www.sciencedirect.com/science/article/pii/S1474442225001577?via=ihub |
| DOI: |
10.1016/S1474-4422(25)00157-7 |
| Availability: |
https://hdl.handle.net/11585/1039095; https://doi.org/10.1016/S1474-4422(25)00157-7; https://www.sciencedirect.com/science/article/pii/S1474442225001577?via=ihub |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY) ; license uri:iris.PUB15 |
| Accession Number: |
edsbas.16714666 |
| Database: |
BASE |