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Propagative α-synuclein seeds as serum biomarkers for synucleinopathies

Nature Medicine, ISSN: 1546-170X, Vol: 29, Issue: 6, Page: 1448-1455
2023
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Article Description

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.

Bibliographic Details

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

Springer Science and Business Media LLC

Biochemistry, Genetics and Molecular Biology

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