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

Abstract 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 se...

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Main Authors: Anja Schaffrath, Sophia Schleyken, Aline Seger, Hannah Jergas, Pelin Özdüzenciler, Marlene Pils, Lara Blömeke, Anneliese Cousin, Johannes Willbold, Tuyen Bujnicki, Oliver Bannach, Gereon R. Fink, Dieter Willbold, Michael Sommerauer, Michael T. Barbe, Gültekin Tamgüney
Format: Article
Language:English
Published: Nature Portfolio 2023-02-01
Series:npj Parkinson's Disease
Online Access:https://doi.org/10.1038/s41531-023-00458-4
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author Anja Schaffrath
Sophia Schleyken
Aline Seger
Hannah Jergas
Pelin Özdüzenciler
Marlene Pils
Lara Blömeke
Anneliese Cousin
Johannes Willbold
Tuyen Bujnicki
Oliver Bannach
Gereon R. Fink
Dieter Willbold
Michael Sommerauer
Michael T. Barbe
Gültekin Tamgüney
author_facet Anja Schaffrath
Sophia Schleyken
Aline Seger
Hannah Jergas
Pelin Özdüzenciler
Marlene Pils
Lara Blömeke
Anneliese Cousin
Johannes Willbold
Tuyen Bujnicki
Oliver Bannach
Gereon R. Fink
Dieter Willbold
Michael Sommerauer
Michael T. Barbe
Gültekin Tamgüney
author_sort Anja Schaffrath
collection DOAJ
description Abstract 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.
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spelling doaj.art-af42695f51354555a4c7b28b085dd3962023-11-02T09:43:27ZengNature Portfolionpj Parkinson's Disease2373-80572023-02-019111110.1038/s41531-023-00458-4Patients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stoolAnja Schaffrath0Sophia Schleyken1Aline Seger2Hannah Jergas3Pelin Özdüzenciler4Marlene Pils5Lara Blömeke6Anneliese Cousin7Johannes Willbold8Tuyen Bujnicki9Oliver Bannach10Gereon R. Fink11Dieter Willbold12Michael Sommerauer13Michael T. Barbe14Gültekin Tamgüney15Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichDepartment of Neurology, Faculty of Medicine and University Hospital Cologne, University of CologneDepartment of Neurology, Faculty of Medicine and University Hospital Cologne, University of CologneDepartment of Neurology, Faculty of Medicine and University Hospital Cologne, University of CologneInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichDepartment of Neurology, Faculty of Medicine and University Hospital Cologne, University of CologneInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichDepartment of Neurology, Faculty of Medicine and University Hospital Cologne, University of CologneDepartment of Neurology, Faculty of Medicine and University Hospital Cologne, University of CologneInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum JülichAbstract 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.https://doi.org/10.1038/s41531-023-00458-4
spellingShingle Anja Schaffrath
Sophia Schleyken
Aline Seger
Hannah Jergas
Pelin Özdüzenciler
Marlene Pils
Lara Blömeke
Anneliese Cousin
Johannes Willbold
Tuyen Bujnicki
Oliver Bannach
Gereon R. Fink
Dieter Willbold
Michael Sommerauer
Michael T. Barbe
Gültekin Tamgüney
Patients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stool
npj Parkinson's Disease
title Patients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stool
title_full Patients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stool
title_fullStr Patients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stool
title_full_unstemmed Patients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stool
title_short Patients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stool
title_sort patients with isolated rem sleep behavior disorder have elevated levels of alpha synuclein aggregates in stool
url https://doi.org/10.1038/s41531-023-00458-4
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