Details

Autor(en) / Beteiligte

• 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

Titel

Propagative α-synuclein seeds as serum biomarkers for synucleinopathies

Ist Teil von

• Nature medicine, 2023-06, Vol.29 (6), p.1448-1455

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.