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

Misfolded and aggregated alpha-synuclein is a neuropathological hallmark of Parkinson's disease (PD). Thus, alpha-synuclein aggregates are regarded as a biomarker for the development of diagnostic assays. Quantification of alpha-synuclein aggregates in body fluids is challenging, and requires highly sensitive and specific assays. Recent studies suggest that alpha-synuclein aggregates may be shed into stool. We used surface-based fluorescence intensity distribution analysis (sFIDA) to detect and quantify single particles of alpha-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 alpha-synuclein aggregates in stool of iRBD patients versus those of controls (p = 0.024) or PD patients (p < 0.001). Our results show that alpha-synuclein aggregates are excreted in stool and can be measured using the sFIDA assay, which could support the diagnosis of prodromal synucleinopathies.

Automated summary

This study used surface-based fluorescence intensity distribution analysis (sFIDA) to detect and quantify single particles of alpha-synuclein aggregates in stool samples of 94 PD patients, 72 isolated rapid eye movement sleep behavior disorder (iRBD) patients, and 51 healthy controls. The results showed significantly elevated concentrations of alpha-synuclein aggregates in stool samples of iRBD patients compared to controls (p = 0.024) or PD patients (p < 0.001). The study suggests that measuring alpha-synuclein aggregates in stool using the sFIDA assay could support the diagnosis of prodromal synucleinopathies.