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Detail of ExtFig2b_CSF

Ayami Okuzumi, Taku Hatano, Gen Matsumoto, Shuko Nojiri, Shin-Ichi Ueno, Yoko Imamichi-Tatano, Haruka Kimura, Soichiro Kakuta, Akihide Kondo, Takeshi Fukuhara, Yuanzhe Li, Manabu Funayama, Shinji Saiki, Daisuke Taniguchi, Taiji Tsunemi, Deborah McIntyre, Jean-Jacques Gerardy, Michel Mittelbronn, Rejko Kruger, Yasuo Uchiyama, Nobuyuki Nukina, Nobutaka Hattori (2023) Propagative alpha-synuclein seeds as serum biomarkers for synucleinopathies., Nature medicine

Published in 2023 May 29 (Electronic publication in May 29, 2023, midnight )

• doi: 10.1038/s41591-023-02358-9
• pmid: 37248302
  

(Abstract) Abnormal alpha-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 beta-sheet seed conformation of alpha-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 alpha-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.