Session Information
Date: Monday, October 8, 2018
Session Title: Parkinson's Disease: Pathophysiology
Session Time: 1:15pm-2:45pm
Location: Hall 3FG
Objective: The goals of this study were to create a highly sensitive brightfield immunohistochemical (IHC) assay for pathological alpha-synuclein (aSyn) in formalin-fixed, paraffin embedded (FFPE) tissue biopsies and test the assay in a proof-of-concept study with post-mortem tissues from 20 Parkinson’s disease (PD) and 20 non-PD individuals.
Background: Development of therapeutic agents for PD is hampered by a lack of diagnostic tests that accurately identify patients with PD, especially early PD. While the definitive diagnosis of PD could only be made at autopsy upon demonstration of pathological central nervous system aSyn, recent findings have demonstrated pathological aSyn in the peripheral nervous system, making it theoretically possible to test for its presence via skin punch biopsies.
Methods: The IHC assay detected pathological aSyn using a highly sensitive and specific rabbit monoclonal antibody. A novel chromogenic detection method was developed to enable high contrast visualization of pathological aSyn in nerves. The entire assay procedure was performed on the completely automated BenchMark ULTRA slide staining system. Precision and specificity of the assay were validated in a CAP/CLIA-compliant environment. The assay was developed using post-mortem skin, submandibular gland, and colon tissue from patients whose PD status had been confirmed by accepted clinicopathological diagnostic criteria. Proof-of-concept of the assay was tested with post-mortem abdomen skin samples from a cohort of 20 PD and 20 non-PD subjects.
Results: Pathological aSyn staining was observed in peripheral nerves in the post-mortem abdomenal skin samples of 17 PD and 0 non-PD samples. There was a high degree of association between presence of pathological aSyn staining and PD status (Pearson chi-square value = 29.565 with DF = 1 and p-Value < 0.0001). Assay specificity was 100%.
Conclusions: A novel IHC assay was developed to detect aSyn pathology associated with PD in the peripheral tissue. This tool has the potential to be developed into a diagnostic assay for synucleinopathies and selection of patients for clinical trials targeting aggregated alpha-synuclein.
To cite this abstract in AMA style:
TS. Tsao, A. Racolta, H. Zhang, M. Robida, J. Pugh, T. Beach, T. Kremer, C. Czech, K. Taylor, W. Zago, L. Pestic-Dragovich, L. Tang, S. Dziadek. Automated immunohistochemical detection of pathological alpha-synuclein in human tissue biopsy [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/automated-immunohistochemical-detection-of-pathological-alpha-synuclein-in-human-tissue-biopsy/. Accessed June 14, 2025.« Back to 2018 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/automated-immunohistochemical-detection-of-pathological-alpha-synuclein-in-human-tissue-biopsy/