Evaluation of submandibular gland biopsies with RT-QuIC in Parkinson's disease under investigation

BackgroundThe definite diagnosis of Parkinsons disease (PD) is usually made by the detection of -synuclein aggregates in the brain post mortem with the rare exception of some genetic forms. Traces of -synuclein aggregates in extracerebral tissue biopsies may serve as an appropriate biomarker to confirm a clinical diagnosis in vivo. ObjectivesWe set out to determine whether the detection of -synuclein aggregates in submandibular gland biopsies is an effective means for diagnosing PD patients. MethodsWe examined submandibular gland biopsies from 25 patients with PD under investigation and 25 age-matched controls to detect -synuclein aggregates using real-time quaking induced conversion (RT-QuIC) as a seed amplification-assay and immunohistochemical -synuclein aggregate detection and paraffin-embedded tissue blot (PET-blot) as confirmatory methods. ResultsOur RT-QuIC assay detected -synuclein aggregates in submandibular gland biopsies with a sensitivity of 81,1%, which increased to 90% after a clinical follow-up, and a specificity of 100%. The PET-blot with mAb5C12 confirmed 50% of the RT-QuIC positives and offered a sensitivity of 45,8% (50% after clinical follow-up) and a specificity of 100%. Immunohistochemical detection using the same antibody confirmed 28% of the RT-QuIC positives, but found two of the controls to be positive and therefore provided a sensitivity of 26,1% (28,6% after clinical follow-up) and a specificity of 92%. ConclusionsThe RT-QuIC Assay demonstrated comparable sensitivity to the clinical diagnosis (when neuropathologic examination represents the gold standard) and exhibited a similar level of specificity as the PET-blot.