Bibliographic Details
| Title: |
Propagative α-synuclein seeds as serum biomarkers for synucleinopathies |
| Authors: |
Okuzumi, Ayami, Hatano, Taku, Matsumoto, Gen, Nojiri, Shuko, Ueno, Shin-ichi, Imamichi-Tatano, Yoko, Kimura, Haruka, Kakuta, Soichiro, Kondo, Akihide, Fukuhara, Takeshi, Li, Yuanzhe, Funayama, Manabu, Saiki, Shinji, Taniguchi, Daisuke, Tsunemi, Taiji, McIntyre, Deborah, Gérardy, Jean-Jacques, Mittelbronn, Michel, Kruger, Rejko, Uchiyama, Yasuo, Nukina, Nobuyuki, Hattori, Nobutaka |
| Source: |
Nature Medicine; 20240101, Issue: Preprints p1-8, 8p |
| Abstract: |
Abnormal α-synuclein aggregation is a key pathological feature of a group of neurodegenerative diseases known as synucleinopathies, which include Parkinson’s disease (PD), dementia with Lewy bodies and multiple system atrophy (MSA). The pathogenic β-sheet seed conformation of α-synuclein is found in various tissues, suggesting potential as a biomarker, but few studies have been able to reliably detect these seeds in serum samples. In this study, we developed a modified assay system, called immunoprecipitation-based real-time quaking-induced conversion (IP/RT-QuIC), which enables the detection of pathogenic α-synuclein seeds in the serum of individuals with synucleinopathies. In our internal first and second cohorts, IP/RT-QuIC showed high diagnostic performance for differentiating PD versus controls (area under the curve (AUC): 0.96 (95% confidence interval (CI) 0.95–0.99)/AUC: 0.93 (95% CI 0.84–1.00)) and MSA versus controls (AUC: 0.64 (95% CI 0.49–0.79)/AUC: 0.73 (95% CI 0.49–0.98)). IP/RT-QuIC also showed high diagnostic performance in differentiating individuals with PD (AUC: 0.86 (95% CI 0.74–0.99)) and MSA (AUC: 0.80 (95% CI 0.65–0.97)) from controls in a blinded external cohort. Notably, amplified seeds maintained disease-specific properties, allowing the differentiation of samples from individuals with PD versus MSA. In summary, here we present a novel platform that may allow the detection of individuals with synucleinopathies using serum samples. |
| Database: |
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