The diagnosis of neurodegenerative disorders (NDDs) poses a grand challenge for clinicians, as many diseases show overlapping symptoms.^{Reference Das, Zhang and Ang1} Although biomarkers of neuronal and synaptic damage together with imaging approaches and clinical evaluation may facilitate diagnosis, the lack of sensitive and specific assays hampers early and accurate diagnosis and follow-up.

Seeded aggregation assays have gained considerable attention for their ability to amplify in vitro protein aggregates associated with different NDDs. Among these, quaking-induced conversion (QuIC) assays represent the most promising tools for NDD diagnosis, with Prion disorders (PDs) leading methodological advancements,^{Reference Salciccia, Costanzo and Ruocco2} as demonstrated by the inclusion of real-time QuIC (RT-QuIC) in the diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD).^{Reference Hermann, Appleby and Brandel3} However, the need for specialized BSL-2/BSL-3 laboratories equipped with an all-in-one device, comprising a fluorescent reader, a shaker and a thermomixer, thwarts the widespread use of RT-QuIC for PDs.

In this number of CJNS, Slota and co-workers apply a simplified version of RT-QuIC, termed end-point QuIC (EP-QuIC),^{Reference Slota, Myskiw and Peterson4} to more than 2500 CSF samples from Canadian patients showing rapid cognitive decline. Based on this testing, they estimate the incidence of sCJD in Canada at 1.51 × 10^–6, consistent with worldwide incidence.^{Reference Uttley, Carroll, Wong, Hilton and Stevenson5} This is a surprising and encouraging result, as the CSF samples came from subjects with a generic NDD clinical picture, not from patients with a precise suspicion of CJD.

Notably, in EP-QuIC, a heating mixer for 96-well plates is used to amplify protein aggregates, and a common fluorescence reader for thioflavin T is employed to read the signal at the endpoint, overcoming the need for expensive machinery and highly skilled operators required for RT-QuIC. However, this simplicity makes EP-QuIC less informative than RT-QuIC, which yields typical kinetic aggregation curves that can be precious for challenging samples and to discriminate amyloid strains.^{Reference Schmitz, Candelise and Canaslan6}

Overall, this study highlights EP-QuIC as a user-friendly, automatable and relatively cheap methodology for high-throughput screening of samples from suspected NDD cases, paving the way for earlier diagnosis of these devastating pathologies. The obvious step forward is to subject EP-QuIC to validation studies (ring trials, retrospective and prospective investigations) as was done for RT-QuIC.^{Reference Hermann, Appleby and Brandel3} Given its potential field applicability, we suggest testing EP-QuIC performance not only across different types of sCJD and other human PDs but also on animal PDs such as chronic wasting disease that is nowadays a concern in Canada and other Northern Hemisphere countries.