| Title |
Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson’s disease
|
|---|---|
| Published in |
Acta Neuropathologica, February 2017
|
| DOI | 10.1007/s00401-017-1684-z |
| Pubmed ID | |
| Authors |
Kathrin Doppler, Hanna-Maria Jentschke, Lena Schulmeyer, David Vadasz, Annette Janzen, Markus Luster, Helmut Höffken, Geert Mayer, Joachim Brumberg, Jan Booij, Thomas Musacchio, Stephan Klebe, Elisabeth Sittig-Wiegand, Jens Volkmann, Claudia Sommer, Wolfgang H. Oertel |
| Abstract |
Phosphorylated alpha-synuclein (p-alpha-syn) deposits, one of the neuropathological hallmarks of Parkinson's disease (PD), have recently been detected in dermal nerve fibres in PD patients with good specificity and sensitivity. Here, we studied whether p-alpha-syn may serve as a biomarker in patients with a high risk of developing PD, such as those with REM sleep behaviour disorder (RBD). We compared the presence and distribution of p-alpha-syn deposits in dermal nerve fibres in 18 patients with RBD, 25 patients with early PD and 20 normal controls. Skin biopsy was taken at C7, Th10, and the upper and lower leg. Presynaptic dopamine transporter imaging using FP-CIT-SPECT was performed in all patients with RBD and in 11 patients with PD. All RBD patients underwent olfactory function testing. The likelihood ratio (LR) for prodromal PD was calculated for each patient based on published research criteria. Skin serial sections were assessed by double-immunofluorescence labelling with antibodies to pSer129-alpha-syn under blinded conditions. P-alpha-syn was visualized in 10/18 patients with RBD (sensitivity of 55.6%) and in 20/25 early PD patients (sensitivity of 80%) but in none of the controls (specificity of 100%). The percentage of dermal structures innervated by p-alpha-syn-positive fibres was negatively correlated with dopamine transporter binding in the FP-CIT-SPECT (ρ = -0.377, p = 0.048), with olfactory function (ρ = -0.668, p = 0.002), and positively correlated with the total LR for RBD to present prodromal PD (ρ = 0.531, p = 0.023). Dermal p-alpha-syn can be considered a peripheral histopathological marker of synucleinopathy and can be detected in a subgroup of RBD patients presumably representing prodromal PD. Dermal p-alpha-syn is detectable in RBD patients without PD motor symptoms, thereby stratifying a patient group that is of great interest for clinical trials testing disease-modifying drugs. |
X Demographics
The data shown below were collected from the profiles of 9 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 2 | 22% |
| Canada | 1 | 11% |
| Germany | 1 | 11% |
| Spain | 1 | 11% |
| Unknown | 4 | 44% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 7 | 78% |
| Practitioners (doctors, other healthcare professionals) | 2 | 22% |
Mendeley readers
The data shown below were compiled from readership statistics for 233 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 1 | <1% |
| Unknown | 232 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 33 | 14% |
| Student > Ph. D. Student | 31 | 13% |
| Student > Doctoral Student | 25 | 11% |
| Student > Master | 23 | 10% |
| Student > Bachelor | 22 | 9% |
| Other | 48 | 21% |
| Unknown | 51 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 63 | 27% |
| Neuroscience | 51 | 22% |
| Agricultural and Biological Sciences | 17 | 7% |
| Psychology | 11 | 5% |
| Biochemistry, Genetics and Molecular Biology | 10 | 4% |
| Other | 17 | 7% |
| Unknown | 64 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 91. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 November 2023.
All research outputs
#452,893
of 24,981,585 outputs
Outputs from Acta Neuropathologica
#50
of 2,512 outputs
Outputs of similar age
#10,225
of 430,711 outputs
Outputs of similar age from Acta Neuropathologica
#3
of 38 outputs
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