Combining skin and olfactory α-synuclein seed amplification assays (SAA)-towards biomarker-driven phenotyping in synucleinopathies.

Autor: Kuzkina A; University Hospital Würzburg (UKW), Department of Neurology, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. akuzkina@bwh.harvard.edu.; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA. akuzkina@bwh.harvard.edu.; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital, Boston, MA, 02115, USA. akuzkina@bwh.harvard.edu., Rößle J; University Hospital Würzburg (UKW), Department of Neurology, Josef-Schneider-Str. 11, 97080, Würzburg, Germany., Seger A; University Hospital Cologne, Department of Neurology, Faculty of Medicine, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany., Panzer C; University Hospital Würzburg (UKW), Department of Neurology, Josef-Schneider-Str. 11, 97080, Würzburg, Germany., Kohl A; University Hospital Würzburg (UKW), Department of Neurology, Josef-Schneider-Str. 11, 97080, Würzburg, Germany., Maltese V; University Hospital Würzburg (UKW), Department of Neurology, Josef-Schneider-Str. 11, 97080, Würzburg, Germany., Musacchio T; University Hospital Würzburg (UKW), Department of Neurology, Josef-Schneider-Str. 11, 97080, Würzburg, Germany., Blaschke SJ; University Hospital Cologne, Department of Neurology, Faculty of Medicine, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany., Tamgüney G; Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225, Düsseldorf, Germany.; Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany., Kaulitz S; University Hospital Würzburg (UKW), Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Josef-Schneider-Str. 11, 97080, Würzburg, Germany., Rak K; University Hospital Würzburg (UKW), Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Josef-Schneider-Str. 11, 97080, Würzburg, Germany., Scherzad A; University Hospital Würzburg (UKW), Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Josef-Schneider-Str. 11, 97080, Würzburg, Germany., Zimmermann PH; University of Cologne, Medical Faculty, Department of Otorhinolaryngology, Head and Neck Surgery, Kerpener Strasse 62, 50931, Cologne, Germany.; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine, University Hospital Cologne, Robert-Koch-Strasse 21, 50931, Cologne, Germany., Klussmann JP; University of Cologne, Medical Faculty, Department of Otorhinolaryngology, Head and Neck Surgery, Kerpener Strasse 62, 50931, Cologne, Germany.; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine, University Hospital Cologne, Robert-Koch-Strasse 21, 50931, Cologne, Germany., Hackenberg S; University Hospital Würzburg (UKW), Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.; RWTH Aachen University, Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Aachen, Germany., Volkmann J; University Hospital Würzburg (UKW), Department of Neurology, Josef-Schneider-Str. 11, 97080, Würzburg, Germany., Sommer C; University Hospital Würzburg (UKW), Department of Neurology, Josef-Schneider-Str. 11, 97080, Würzburg, Germany., Sommerauer M; University Hospital Cologne, Department of Neurology, Faculty of Medicine, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; Institute of Neuroscience and Medicine (INM-3), Forschungszentrum Jülich, Jülich, Germany., Doppler K; University Hospital Würzburg (UKW), Department of Neurology, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. doppler_k@ukw.de.
Jazyk: angličtina
Zdroj: NPJ Parkinson's disease [NPJ Parkinsons Dis] 2023 May 29; Vol. 9 (1), pp. 79. Date of Electronic Publication: 2023 May 29.
DOI: 10.1038/s41531-023-00519-8
Abstrakt: Seed amplification assays (SAA) are becoming commonly used in synucleinopathies to detect α-synuclein aggregates. Studies in Parkinson's disease (PD) and isolated REM-sleep behavior disorder (iRBD) have shown a considerably lower sensitivity in the olfactory epithelium than in CSF or skin. To get an insight into α-synuclein (α-syn) distribution within the nervous system and reasons for low sensitivity, we compared SAA assessment of nasal brushings and skin biopsies in PD (n = 27) and iRBD patients (n = 18) and unaffected controls (n = 30). α-syn misfolding was overall found less commonly in the olfactory epithelium than in the skin, which could be partially explained by the nasal brushing matrix exerting an inhibitory effect on aggregation. Importantly, the α-syn distribution was not uniform: there was a higher deposition of misfolded α-syn across all sampled tissues in the iRBD cohort compared to PD (supporting the notion of RBD as a marker of a more malignant subtype of synucleinopathy) and in a subgroup of PD patients, misfolded α-syn was detectable only in the olfactory epithelium, suggestive of the recently proposed brain-first PD subtype. Assaying α-syn of diverse origins, such as olfactory (part of the central nervous system) and skin (peripheral nervous system), could increase diagnostic accuracy and allow better stratification of patients.
(© 2023. The Author(s).)
Databáze: MEDLINE
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