Quantitative measures of total and phosphorylated alpha-synuclein in skin tissue as potential biomarkers for synucleinopathies
Bram L. van der Gaag (Vrije Universiteit Amsterdam, Amsterdam UMC)
Janna van Wetering (Amsterdam UMC, Vrije Universiteit Amsterdam)
Martino L. Morella (Amsterdam UMC, Vrije Universiteit Amsterdam)
Johannes Jp Breve (Vrije Universiteit Amsterdam, Amsterdam UMC)
Niels Reijner (Amsterdam UMC, Vrije Universiteit Amsterdam)
Jenna Pfeifer (Amsterdam UMC, TU Delft - Mechanical Engineering)
Amador Simando (William H. Quasha Memorial, Quezon, De La Salle University, Amsterdam UMC)
J. J. van Hilten (Leiden University Medical Center)
Henk W. Berendse (Amsterdam UMC, Vrije Universiteit Amsterdam)
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Abstract
BackgroundAlpha-synuclein can be detected in skin biopsies of individuals with synucleinopathies. However, quantitative data of total and phosphorylated Serine 129 (pS129) alpha-synuclein in skin biopsies are scarce.ObjectiveWe aimed to investigate the biomarker potential of quantitative total and pS129 alpha-synuclein measurements in skin biopsies from people with synucleinopathies and controls.MethodsWe developed and validated AlphaLISA™ immunoassays to determine total and pS129 alpha-synuclein concentrations. Postmortem skin biopsies of Parkinson's disease (PD: n = 18), Dementia with Lewy bodies (DLB: n = 3), Multiple System Atrophy (MSA: n = 5) and control (n = 5) subjects were collected at the cervical vertebra C7. Brain tissues (middle temporal gyrus and substantia nigra) were collected from these same cases. In addition, skin biopsies of controls (n = 20) and PD cases (n = 40) were obtained from the ProPark cohort.ResultsTotal and pSer129 alpha-synuclein could be robustly detected and quantified in all skin samples. We observed a trend towards increased total (+58%, p = 0.055) and pS129 (+131%, p = 0.060) alpha-synuclein skin concentrations in synucleinopathy cases compared to controls. We found no correlations between pS129 alpha-synuclein concentrations in paired brain and skin tissues from the same donors. pS129 alpha-synuclein concentrations were similar for clinical PD cases and controls and there was no correlation with motor symptom severity (UPDRS-III).ConclusionsThese findings highlight that total and pS129 alpha-synuclein can be biochemically quantified in skin biopsies, but warrant further validation and investigation to asses its potential as a diagnostic biomarker in clinical cohorts.
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