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Doppler, K.* ; Jentschke, H.* ; Schulmeyer, L.* ; Vadasz, D.* ; Janzen, A.* ; Luster, M.* ; Hoeffken, H.* ; Mayer, G.* ; Brumberg, J.* ; Booij, J.* ; Musacchio, T.* ; Klebe, S.* ; Sittig-Wiegand, E.* ; Volkmann, J.* ; Sommer, C.* ; Oertel, W.H.

Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson's disease.

Acta Neuropathol. 133, 535-545 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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-alphasyn 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 (rho = -0.377, p = 0.048), with olfactory function (rho = -0.668, p = 0.002), and positively correlated with the total LR for RBD to present prodromal PD (rho = 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Rem Sleep Behaviour Disorder ; Parkinson's Disease ; Alpha-synuclein ; Skin Biopsy ; Fp-cit-spect; Multiple System Atrophy; Mds Research Criteria; Lewy-body Disease; Brain Pathology; Spect; Progression
ISSN (print) / ISBN 0001-6322
e-ISSN 1432-0533
Journal Acta Neuropathologica
Quellenangaben Volume: 133, Issue: 4, Pages: 535-545 Article Number: , Supplement: ,
Publisher Springer
Publishing Place New York
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Neurogenomics (ING)