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

AbstractPhosphorylated 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 pat ients 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 f ibres 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 positiv...
Source: Acta Neuropathologica - Category: Neurology Source Type: research