Association of α-synuclein seed-amplification kinetics with cognitive decline in idiopathic Parkinson's disease
Rodríguez Antigüedad, Jon (Universitat Autònoma de Barcelona. Departament de Medicina)
Puig-Davi, Arnau (Institut de Recerca Sant Pau)
Ruiz Barrio, Iñigo (Institut de Recerca Sant Pau)
Campo-Caballero, David (Biodonostia Osasun Ikerketako Institutura (País Basc))
Vacchi, Elena (Università della Svizzera Italiana)
Melli, Giorgia (Università della Svizzera Italiana)
Bojtos, Lidia (Institut de Recerca Sant Pau)
Franch-Marti, Carla (Institut de Recerca Sant Pau)
Olmedo-Saura, Gonzalo (Institut de Recerca Sant Pau)
Vázquez-Oliver, Anna (Institut de Recerca Sant Pau)
Martínez-Horta, Saul (Institut de Recerca Sant Pau)
Kulisevsky, Jaime (Institut de Recerca Sant Pau)
Pagonabarraga Mora, Javier (Institut de Recerca Sant Pau)

Fecha:	2026
Resumen:	Introduction: Neurodegeneration and α-synuclein aggregates are pathological hallmarks of Parkinson's disease (PD). The α-synuclein seed-amplification assay (SAA) is a robust diagnostic tool for synucleinopathies. However, its binary readout limits its utility, and associations between semi-quantitative parameters and clinical outcomes remain inconsistent. This cohort study investigated whether baseline CSF α-synuclein SAA kinetic parameters are associated with longitudinal clinical trajectories in PD. Methods: A total of 898 participants with idiopathic PD and positive α-synuclein SAA (24-h protocol) from the Parkinson's Progression Markers Initiative (PPMI) cohort were included. Results: Linear mixed-effects models showed that higher maximum fluorescence, area under the fluorescence curve, and maximum slope at baseline visit were significantly associated with slower cognitive decline, both globally and across specific cognitive domains. In exploratory analyses, a similar, though less consistent, pattern was observed for motor progression. Results were consistent in sensitivity analyses restricted to participants with at least five years of follow-up (n = 309). Conclusion: The main findings of this study suggest that higher baseline amplitude-related parameters on CSF α-synuclein SAA are associated with less pronounced long-term cognitive decline in a subset of PD patients. These results should be interpreted with caution, and further studies are needed to determine whether these observations reflect methodological limitations of the assay or biologically meaningful differences in α-synuclein aggregation.
Nota:	Altres ajuts: acords transformatius de la UAB
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Parkinson's disease ; CSF ; Seed-amplification assay ; α-synuclein ; Cognitive decline
Publicado en:	Parkinsonism and Related Disorders, Vol. 150 (September 2026) , art. 108856, ISSN 1873-5126

DOI: 10.1016/j.parkreldis.2026.108856
PMID: 42492163

7 p, 728.7 KB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Recerca Sant Pau
Artículos > Artículos de investigación
Artículos > Artículos publicados