Combining skin and olfactory α-synuclein RT-QuIC - towards biomarker-driven phenotyping in synucleinopathies

Autor: Anastasia Kuzkina, Jonas Rößle, Aline Seger, Celine Panzer, Antonia Kohl, Virginia Maltese, Thomas Musacchio, Stefan Blaschke, Gültekin Tamgüney, Stefan Kaulitz, Kristen Rak, Agmal Scherzad, Philipp Zimmermann, Jens Klussmann, Stefan Hackenberg, Jens Volkmann, Claudia Sommer, Michael Sommerauer, Kathrin Doppler
Rok vydání: 2022
Popis: Seeding assays, such as real-time quaking-induced conversion (RT-QuIC), 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 RT-QuIC assessment of nasal brushings and skin biopsies in PD and iRBD patients and unaffected controls. We could show higher sensitivity of RT-QuIC in skin compared to nasal brushings and a higher deposition of misfolded α-synuclein 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. Interestingly, we identified a PD subgroup of patients with misfolded α-syn in the olfactory epithelium who did not show any dermal pathology, likely corresponding to the recently proposed brain-first subtype. Assaying α-syn of diverse origin (such as olfactory and peripheral nervous system) could allow better stratification of patients.
Databáze: OpenAIRE