Objective: To evaluate pathologic alpha-synuclein (AS) seeding activity with Real-time quaking-induced conversion (RT-QuIC) assay using formalin fixed paraffine-embedded (FFPE) tissue of GI tract in Parkinson’s disease (PD) patients.
Background: The use of AS aggregation in peripheral tissues of PD as a pathologic biomarker has an issue with low sensitivity. RT-QuIC assay has shown seeding activity of pathologic AS using peripheral tissues in PD. However, there has been no study using RT-QuIC assay with gastrointestinal (GI) tract tissue to date.
Method: This study was conducted in two parts: Part I. preliminary autopsy study included four autopsy-confirmed patients with synucleinopathy (PD 2, dementia with Lewy bodies [DLB] 1, and multiple system atrophy [MSA] 1) and two normal autopsy controls. Frozen and FFPE tissues of the brain were obtained from the brain bank. Part II. clinical case-control study included 20 clinically diagnosed PD patients, and matched controls. Surgically resected FFPE tissues from the upper and lower GI tracts were used. RT-QuIC assay was performed to evaluate pathologic seed amplification using frozen or FFPE tissues. The presence or absence of AS aggregation was confirmed by conventional phosphorylated AS (pAS) immunohistochemistry (IHC).
Results: In Part I, RT-QuIC assay showed pathologic AS amplification in frozen and FFPE brain tissues of PD and DLB patients, and FFPE stomach tissue of PD patients, but not of a MSA patient and controls. In Part II, pathologic seeding activity was found in 10% (2/20) of the stomach tissues of clinical PD patients, but none of matched controls. IHC showed pAS positive staining in 55% of patients (11/20) and 15% of controls (3/20).
Conclusion: This study showed that the RT-QuIC assay using FFPE tissue of the GI tract was inadequate as a biomarker in PD.
To cite this abstract in AMA style:
C. Shin, JY. Han, YP. Choi, SI. Kim, SH. Park, HK. Yang, HJ. Lee, SH. Kong, YS. Suh, HJ. Kim, B. Jeon. in vivo and autopsy validation of alpha-synuclein seeding activity using RT-QuIC assay in the gastrointestinal tract of patients with Parkinson’s disease [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/in-vivo-and-autopsy-validation-of-alpha-synuclein-seeding-activity-using-rt-quic-assay-in-the-gastrointestinal-tract-of-patients-with-parkinsons-disease/. Accessed June 14, 2025.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/in-vivo-and-autopsy-validation-of-alpha-synuclein-seeding-activity-using-rt-quic-assay-in-the-gastrointestinal-tract-of-patients-with-parkinsons-disease/