2024 American Academy of Neurology Abstract Website

Objective:

In this study, we utilized a seed amplification assay called real-time quaking inducing conversion (RT-QuIC) to determine whether aggregation-prone α-synuclein (α-syn) is present and detectable in submandibular and esophageal tissue of patients with synucleinopathies and whether the kinetics of aggregation differ for these two conditions.

Background:

Parkinson’s disease (PD) and multiple system atrophy (MSA) are neurodegenerative movement disorders involving pathological aggregation of α-syn. The similarity in symptoms between MSA and PD at earlier stages represent a challenge because it can lead to misdiagnosis. Pathologic forms of α-syn (i.e. phosphorylated forms) have been detected in non-CNS tissues as remote as the nerves of the skin and GI tissue.

Design/Methods:

Tissue was obtained from Banner Sun Health Research Institute. We utilized this assay to compare kinetic differences in the pathological aggregation of α-syn present in soluble and insoluble tissue homogenate fractions from submandibular and esophageal tissue of PD (n=5), MSA (n=5) and control (n=5) samples. Conformational specific binding ab (MJFR 14-6-4-2) per total alpha-synuclein levels were measured in soluble and insoluble fractions.

Results:

We were able to distinguish PD from MSA and control samples in both soluble and insoluble fractions. PD samples demonstrated significant differences in kinetics of aggregation (time to threshold) in the RT-QuIC paradigm, even with a small sample size. There were altered levels of conformation-specific alpha-synuclein/total levels seen in soluble and insoluble samples on immunoblot. The kinetics of amplification were consistent in both submandibular and esophageal tissue.

Conclusions:

These results demonstrate that aggregation-prone forms of α-syn are present in GI tissue in PD patients and that RT-QuIC can be utilized to differentiate PD and MSA and non-synucleinopathy patients.