Objective: To investigate whether pathogenic α-synuclein can be detected using real-time quaking-induced conversion (RT-QuIC) in urine-derived neuronal extracellular vesicles (NEVs) as a fully non-invasive biomarker platform for synucleinopathies
Background: α-Synuclein aggregation is a crucial pathological feature of synucleinopathies such as Parkinson’s disease (PD) and multiple system atrophy (MSA). While pathogenic α-synuclein seeds can be detected using real-time quaking-induced conversion (RT-QuIC), current methods mainly depend on cerebrospinal fluid, which is invasive and not ideal for repeated testing or large-scale screening testing.
Method: Urine-derived NEVs were isolated through direct immunoprecipitation using magnetic beads conjugated with L1CAM. The RT-QuIC assay was conducted on samples from 26 patients with Parkinson’s disease (PD), 13 with multiple system atrophy (MSA), and 25 disease controls, which included 16 healthy controls (HC), 4 with progressive supranuclear palsy (PSP), and 5 with normal pressure hydrocephalus (NPH).
Results: Urine-derived NEVs exhibited typical neuronal and exosomal markers, as well as a common extracellular vesicle size distribution. The urine-based RT-QuIC assay differentiated PD from disease controls with 73.1% sensitivity and 84% specificity, and MSA from disease controls with 76.9% sensitivity and 84% specificity. Compared to healthy controls (HC) alone, sensitivity and specificity were 73.1% and 93.8% for PD, and 76.9% and 93.8% for MSA, respectively. Kinetic analysis revealed higher maximum fluorescence intensity and area under the curve (AUC) in PD compared to both disease controls and HC (p < 0.005 in all). MSA also exhibited higher maximum fluorescence intensity than HC and a greater AUC than both disease controls and HC (p < 0.05 in all comparisons).
Conclusion: A fully non-invasive RT-QuIC assay detecting α-synuclein in urine-derived NEV was developed and optimized, demonstrating high specificity and moderate sensitivity for synucleinopathies. Validation in larger cohorts is necessary.
To cite this abstract in AMA style:
HBT. Tran, TA. Nguyen, HJ. Choi, HD. Nguyen, IH. Kwak, DG. Ko, JK. Yu, SJ. Song, JH. Lim, YE. Kim. Urine-derived neuronal extracellular vesicle α-synuclein seed amplification assay for synucleinopathies: a non-invasive biomarker study [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/urine-derived-neuronal-extracellular-vesicle-%ce%b1-synuclein-seed-amplification-assay-for-synucleinopathies-a-non-invasive-biomarker-study/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/urine-derived-neuronal-extracellular-vesicle-%ce%b1-synuclein-seed-amplification-assay-for-synucleinopathies-a-non-invasive-biomarker-study/