Summary
A medRxiv preprint describes a modified endpoint QuIC assay that detected prion seeding activity in sporadic CJD brain samples within six hours, with some results available in two hours. The assay showed 100% sensitivity and specificity in the reported CSF testing.
Researchers in Japan have reported a faster version of a laboratory assay for detecting prion seeding activity associated with sporadic Creutzfeldt–Jakob disease (sCJD). In a medRxiv preprint posted on September 16, 2026, the team said the optimized endpoint quaking-induced conversion assay detected activity in brain samples within six hours, and in some cases within two hours.
The assay also showed 100% sensitivity and 100% specificity in the cerebrospinal-fluid (CSF) testing described in the preprint. The work is a preprint study, so these results are preliminary rather than a completed clinical validation.
Contents
Why prion detection is technically difficult
CJD is a rapidly progressive and fatal neurodegenerative disease linked to the conversion of the normal cellular prion protein, PrPᶜ, into the disease-associated form, PrPˢᶜ. A diagnostic test therefore needs to detect very small amounts of prion-related seeding activity in samples such as CSF or brain tissue.
The established real-time quaking-induced conversion method, or RT-QuIC, amplifies this activity and follows the reaction continuously through fluorescence. According to the researchers, RT-QuIC can provide strong analytical performance but generally requires a plate reader capable of combining high-speed shaking with ongoing fluorescence measurements. Its reaction time can also be prolonged, limiting practical use in routine settings.
How the endpoint assay works
The study focused on endpoint QuIC, or EP-QuIC. Instead of monitoring fluorescence throughout the reaction, EP-QuIC uses vigorous shaking in a ThermoMixer C and records fluorescence once the reaction has ended.
The researchers made minor changes to the assay conditions to improve its speed, robustness and reproducibility. The underlying approach is based on detecting the conversion of recombinant prion protein in the presence of prion seeds from a sample. The fluorescent signal indicates that the conversion reaction has taken place.
A key finding concerned the recombinant PrP used in the reaction. The authors report that some protein batches caused problems for RT-QuIC, including delayed reaction kinetics and spontaneous thioflavin T fluorescence in reactions without a sample seed. In EP-QuIC, those batches did not produce the same reliability problems. Instead, they generated strong and specific fluorescence signals when used to identify sCJD samples.
What the study reported
The optimized EP-QuIC detected prion seeding activity in sporadic CJD brain samples within six hours. Some samples produced detectable results as early as two hours. In the CSF application reported by the authors, the assay achieved 100% sensitivity and 100% specificity.
Sensitivity describes the proportion of affected samples identified by a test, while specificity describes the proportion of samples without the target condition that are correctly classified. The reported combination suggests that the assay performed accurately in the tested set while also shortening the time needed for a result.
A faster endpoint method could make prion-seeding assays easier to fit into diagnostic workflows because it relies on a single fluorescence readout rather than continuous monitoring during shaking. The reported tolerance of different recombinant PrP batches could also reduce one source of assay variability. Together, these features give EP-QuIC potential as a more accessible approach for prion-disease testing.
The supplied preprint page reports percentage performance but does not provide the CSF sample count in its abstract. Broader validation across larger and more diverse patient groups, sample types and laboratories will determine how reliably the result transfers to routine clinical practice.