The Generative Brain

EP-QuIC (endpoint quaking-induced conversion, CSF), Canadian accredited assay

Detects: seeding activity of misfolded prion protein. Sample: cerebrospinal fluid by lumbar puncture, frozen and shipped on dry ice. Stage: accredited clinical service, the national reference CSF prion test in Canada since 2016. EP-QuIC is the Canadian national prion laboratory's version of the QuIC seeding assay. Instead of reading fluorescence every cycle in a plate reader as RT-QuIC does, it shakes the plate in a benchtop ThermoMixer and reads only at the start and at the end. The Winnipeg group chose this format for practical reasons: plate readers wear out at the shaking speed the assay needs, and a ThermoMixer is cheaper and fits in a containment laboratory. It uses hamster recombinant prion protein, the same substrate family as first generation RT-QuIC, which is why it detects sporadic CJD very well but misses part of the inherited spectrum, notably FFI D178N. It is the direct parent and benchmark of ES-QuIC, the deer mouse substrate version published in 2026. Information only, not advice.

Key facts

  • The Prion Diseases Section of the National Microbiology Laboratory in Winnipeg lists a Cerebrospinal Fluid EP-QuIC Test as accredited testing for pathogenic prion protein in CSF; the listing names no RT-QuIC, ES-QuIC, 14-3-3 or tau test.
  • The 2016 introduction paper used hamster recombinant prion protein (residues 23 to 231), 15 microlitres of CSF per reaction, 42 degrees with 900 rpm shaking in a Thermomixer, and a positive call at a fourfold rise in 2 of 3 replicates; the endpoint format was chosen because sustained 900 rpm shaking damages plate readers.
  • On 91 retrospective samples (45 confirmed CJD, 43 sporadic and 2 genetic; 46 non-CJD) EP-QuIC gave 98 percent sensitivity and 91 percent specificity, against 96 and 98 percent for RT-QuIC and 84 and 70 percent for 14-3-3 on the same set; the authors note the thresholds were set on the same data and the study was single laboratory.
  • A 2018 letter showed sporadic CJD samples reached a saturated signal by 47 hours in the ThermoMixer, with a twofold cutoff matching 90 hour RT-QuIC on a small set; the original protocol read at 90 hours.
  • In a prospective Canadian series of 623 analysed CSF samples (April 2017 to June 2019) positive predictive values were 96 percent for EP-QuIC, 68 percent for 14-3-3 gamma and 66 percent for total tau. The same paper states the assays are accredited under ISO/IEC 17025 and free of charge to Canadian health care providers.
  • Across 2016 to 2024 the laboratory ran 2,667 CSF samples by EP-QuIC; sensitivity was 95 percent (267 of 282) in autopsy-confirmed CJD, against 81 percent for 14-3-3 and 91 percent for tau, with 1 false positive among 35 confirmed non-CJD cases. People with disease-causing PRNP mutations were excluded from that analysis.
  • On the 2026 ES-QuIC comparison panel, hamster EP-QuIC detected 101 of 116 cases (87.1 percent): all 61 sporadic CJD cases in Table 1, but only 4 of 13 FFI D178N, 8 of 10 GSS P102L, 3 of 5 VPSPr and neither the A117V nor the V180I case. The text says EP-QuIC has been the accredited Canadian CSF test since 2016, with nearly 3,000 samples tested.
  • Ontario refers CSF to Winnipeg as a CSF Protein Panel with a minimum of 1 ml of clear CSF, frozen and shipped on dry ice, and a stated turnaround of 15 calendar days from receipt.
  • Clinician reports from Western University gave a negative predictive value of 100 percent and a positive predictive value of 83 percent (one false positive, negative on retest) in 2019, and a 2023 case report of a negative first test turning positive on CSF taken about four weeks later.

Timeline

  1. 2016EP-QuIC becomes the accredited Canadian CSF test, per the 2026 ES-QuIC paper.
  2. 2016Introduction paper published online in the Journal of Clinical Microbiology (98 percent sensitivity, 91 percent specificity).
  3. 2017Start of prospective sample collection for the predictive value study (to June 2019).
  4. 2018ThermoMixer letter published, showing results by about 47 hours.
  5. 2019Western University predictive value analysis published.
  6. 2020Prospective study published online (PPV 96 percent against 68 and 66 percent for 14-3-3 gamma and tau).
  7. 2023Case report on repeat EP-QuIC testing published.
  8. 2025Review of 2016 to 2024 Canadian CSF testing published (95 percent sensitivity, 2,667 samples).
  9. 2026ES-QuIC paper published, using EP-QuIC as the 87.1 percent benchmark.
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