biostudies-literatureSchaffrath AElse Kröner-Fresenius-Stiftung (Else Kroner-Fresenius Foundation)Deutsche ForschungsgemeinschaftDeutsche Forschungsgemeinschaft (German Research Foundation)Else Kröner-Fresenius-StiftungParkinson’s FoundationKöln Fortune Programme, Faculty of Medicine, University of CologneParkinson's Foundation (Parkinson's Foundation, Inc.)14https://www.ebi.ac.uk/biostudies/studies/S-EPMC9895074biostudies-literatureUnknown9(1)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.NPJ Parkinson's diseasePatients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stool.PMC98950744315490292019_EKES.02PF-IMP-2022Schleyken SJergas HBannach OFink GRWillbold DWillbold JBujnicki TPils MBarbe MTTamguney GOzduzenciler PSommerauer MSeger ASchaffrath ABlomeke LCousin AfalsePatients 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 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.2023-01-01T00:00:00Z2023 Feb2026-03-17T15:56:26.7Z2025-05-29T19:44:05.696ZS-EPMC98950743673252010.1038/s41531-023-00458-4