Dataset Information
?-Synuclein real-time quaking-induced conversion in the submandibular glands of Parkinson's disease patients.
Ontology highlight
ABSTRACT: Background
Identification of a peripheral biomarker is a major roadblock in the diagnosis of PD. Immunohistological identification of p-serine 129 ?-synuclein in the submandibular gland tissues of PD patients has been recently reported.Objective
We report on a proof-of-principle study for using an ultra-sensitive and specific, real-time quaking-induced conversion assay to detect pathological ?-synuclein in the submandibular gland tissues of PD patients.Methods
The ?-synuclein real-time quaking-induced conversion assay was used to detect and quantify pathological ?-synuclein levels in PD, incidental Lewy body disease, and control submandibular gland tissues as well as in formalin-fixed paraffin-embedded sections.Results
We determined the quantitative seeding kinetics of pathological ?-synuclein present in submandibular gland tissues from autopsied subjects using the ?-synuclein real-time quaking-induced conversion assay. A total of 32 cases comprising 13 PD, 3 incidental Lewy body disease, and 16 controls showed 100% sensitivity and 94% specificity. Interestingly, both PD and incidental Lewy body disease tissues showed 100% concordance for elevated levels of pathological ?-synuclein seeding activity compared to control tissues. End-point dilution kinetic analyses revealed that the submandibular gland had a wide dynamic range of pathological ?-synuclein seeding activity.Conclusions
Our results are the first to demonstrate the utility of using the real-time quaking-induced conversion assay on peripherally accessible submandibular gland tissues and formalin-fixed paraffin-embedded tissue sections to detect PD-related pathological changes with high sensitivity and specificity. Additionally, the detection of seeding activity from incidental Lewy body disease cases containing immunohistochemically undetected pathological ?-synuclein demonstrates the ?-synuclein real-time quaking-induced conversion assay's potential utility for identifying prodromal PD in submandibular gland tissues. © 2019 International Parkinson and Movement Disorder Society.
SUBMITTER: Manne S
PROVIDER: S-EPMC7102508 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Publications
α-Synuclein real-time quaking-induced conversion in the submandibular glands of Parkinson's disease patients.
Movement disorders : official journal of the Movement Disorder Society 20191123 2
<h4>Background</h4>Identification of a peripheral biomarker is a major roadblock in the diagnosis of PD. Immunohistological identification of p-serine 129 α-synuclein in the submandibular gland tissues of PD patients has been recently reported.<h4>Objective</h4>We report on a proof-of-principle study for using an ultra-sensitive and specific, real-time quaking-induced conversion assay to detect pathological α-synuclein in the submandibular gland tissues of PD patients.<h4>Methods</h4>The α-synuc ...[more]