Dermal phospho-alpha-synuclein deposition in patients with Parkinson's disease and mutation of the glucocerebrosidase gene
Please always quote using this URN: urn:nbn:de:bvb:20-opus-222828
- Heterozygous mutations in the glucocerebrosidase gene (GBA1) represent the most common genetic risk factor for Parkinson's disease (PD) and are histopathologically associated with a widespread load of alpha-synuclein in the brain. Therefore, PD patients with GBA1 mutations are a cohort of high interest for clinical trials on disease-modifying therapies targeting alpha-synuclein. There is evidence that detection of phospho-alpha-synuclein (p-syn) in dermal nerve fibers might be a biomarker for the histopathological identification of PD patientsHeterozygous mutations in the glucocerebrosidase gene (GBA1) represent the most common genetic risk factor for Parkinson's disease (PD) and are histopathologically associated with a widespread load of alpha-synuclein in the brain. Therefore, PD patients with GBA1 mutations are a cohort of high interest for clinical trials on disease-modifying therapies targeting alpha-synuclein. There is evidence that detection of phospho-alpha-synuclein (p-syn) in dermal nerve fibers might be a biomarker for the histopathological identification of PD patients even at premotor or very early stages of disease. It is so far unknown whether dermal p-syn deposition can also be found in PD patients with GBA1 mutations and may serve as a biomarker for PD in these patients. Skin biopsies of 10 PD patients with different GBA1 mutations (six N3705, three E326K, one L444P) were analyzed by double-immunofluorescence labeling with anti-p-syn and anti-protein gene product 9.5 (PGP9.5, axonal marker) to detect intraaxonal p-syn deposition. Four biopsy sites (distal, proximal leg, paravertebral Th10, and C7) per patient were studied. P-syn was found in six patients (three N370S, three E326K). P-syn deposition was mainly detected in autonomic nerve fibers, but also in somatosensory fibers and was not restricted to a certain GBA1 mutation. In summary, dermal p-syn in PD patients with GBA1 mutations seems to offer a similar distribution and frequency as observed in patients without a known mutation. Skin biopsy may be suitable to study p-syn deposition in these patients or even to identify premotor patients with GBA1 mutations.…
Author: | Kathrin Doppler, Kathrin Brockmann, Annahita Sedghi, Isabel Wurster, Jens Volkmann, Wolfgang H. Oertel, Claudia Sommer |
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URN: | urn:nbn:de:bvb:20-opus-222828 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Neurologische Klinik und Poliklinik |
Language: | English |
Parent Title (English): | Frontiers in Neurology |
Year of Completion: | 2018 |
Volume: | 9 |
Article Number: | 1094 |
Source: | Frontiers in Neurology (2018) 9:1094. https://doi.org/10.3389/fneur.2018.01094 |
DOI: | https://doi.org/10.3389/fneur.2018.01094 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | Parkinson's disease; alpha-synuclein; biomarker; glucocerebrosidase mutation; skin biopsy |
Release Date: | 2024/07/05 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |