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Open Access 01-12-2024 | Human Prion Disease | Research

Detection limitations of prion seeding activities in blood samples from patients with sporadic prion disease

Authors: Toshiaki Nonaka, Yasushi Iwasaki, Hiroyuki Horiuchi, Katsuya Satoh

Published in: BMC Neurology | Issue 1/2024

Abstract

Background

Human prion diseases (HPDs) are fatal neurodegenerative disorders characterized by abnormal prion proteins (PrPSc). However, the detection of prion seeding activity in patients with high sensitivity remains challenging. Even though real-time quaking-induced conversion (RT-QuIC) assay is suitable for detecting prion seeding activity in a variety of specimens, it shows lower accuracy when whole blood, blood plasma, and blood-contaminated tissue samples are used. In this study, we developed a novel technology for the in vitro amplification of abnormal prion proteins in HPD to the end of enabling their detection with high sensitivity known as the enhanced quaking-induced conversion (eQuIC) assay.

Methods

Three antibodies were used to develop the novel eQUIC method. Thereafter, SD50 seed activity was analyzed using brain tissue samples from patients with prion disease using the conventional RT-QUIC assay and the novel eQUIC assay. In addition, blood samples from six patients with solitary prion disease were analyzed using the novel eQuIC assay.

Results

The eQuIC assay, involving the use of three types of human monoclonal antibodies, showed approximately 1000-fold higher sensitivity than the original RT-QuIC assay. However, when this assay was used to analyze blood samples from six patients with sporadic human prion disease, no prion activity was detected.

Conclusion

The detection of prion seeding activity in blood samples from patients with sporadic prion disease remains challenging. Thus, the development of alternative methods other than RT-QuIC and eQuIC will be necessary for future research.

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Title: Detection limitations of prion seeding activities in blood samples from patients with sporadic prion disease
Authors: Toshiaki Nonaka
Yasushi Iwasaki
Hiroyuki Horiuchi
Katsuya Satoh
Publication date: 01-12-2024
Publisher: BioMed Central
Keyword: Human Prion Disease
Published in: BMC Neurology / Issue 1/2024
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-024-03590-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Detection limitations of prion seeding activities in blood samples from patients with sporadic prion disease

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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