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Patients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stool

Misfolded and aggregated α-synuclein is a neuropathological hallmark of Parkinson’s disease (PD). Thus, α-synuclein aggregates are regarded as a biomarker for the development of diagnostic assays. Quantification of α-synuclein aggregates in body fluids is challenging, and requires highly sensitive a...

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Detalles Bibliográficos
Autores principales: Schaffrath, Anja, Schleyken, Sophia, Seger, Aline, Jergas, Hannah, Özdüzenciler, Pelin, Pils, Marlene, Blömeke, Lara, Cousin, Anneliese, Willbold, Johannes, Bujnicki, Tuyen, Bannach, Oliver, Fink, Gereon R., Willbold, Dieter, Sommerauer, Michael, Barbe, Michael T., Tamgüney, Gültekin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9895074/
https://www.ncbi.nlm.nih.gov/pubmed/36732520
http://dx.doi.org/10.1038/s41531-023-00458-4
Descripción
Sumario:Misfolded and aggregated α-synuclein is a neuropathological hallmark of Parkinson’s disease (PD). Thus, α-synuclein aggregates are regarded as a biomarker for the development of diagnostic assays. Quantification of α-synuclein aggregates in body fluids is challenging, and requires highly sensitive and specific assays. Recent studies suggest that α-synuclein aggregates may be shed into stool. We used surface-based fluorescence intensity distribution analysis (sFIDA) to detect and quantify single particles of α-synuclein aggregates in stool of 94 PD patients, 72 isolated rapid eye movement sleep behavior disorder (iRBD) patients, and 51 healthy controls. We measured significantly elevated concentrations of α-synuclein aggregates in stool of iRBD patients versus those of controls (p = 0.024) or PD patients (p < 0.001). Our results show that α-synuclein aggregates are excreted in stool and can be measured using the sFIDA assay, which could support the diagnosis of prodromal synucleinopathies.