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Updated: Aug 6, 2025
Real-time Quaking-induced Conversion Assay for Detection of CWD Prions in Fecal Material
Published on: September 29, 2017
Real-time quaking-induced conversion assays for prions: Applying a sensitive but imperfect test in clinical practice
Samuel M Jones1, Evelyn B Lazar1,2, Amanda L Porter1
1Mayo Clinic, Department of Neurology, Jacksonville, Florida, USA.
Background And Purpose:
Real-time quaking-induced conversion (RT-QuIC) assays offer a sensitive and specific means for detection of prions, although false negative results are recognized in clinical practice. We profile the clinical, laboratory, and pathologic features associated with false negative RT-QuIC assays and extend these to frame the diagnostic approach to patients with suspected prion disease.
Methods:
A total of 113 patients with probable or definite prion disease were assessed at Mayo Clinic (Rochester, MN; Jacksonville, FL; Scottsdale, AZ) or Washington University School of Medicine (Saint Louis, MO) from 2013 to 2021. RT-QuIC testing for prions was performed in cerebrospinal fluid (CSF) at the National Prion Disease Pathology Surveillance Center (Cleveland, OH).
Results:
Initial RT-QuIC testing was negative in 13 of 113 patients (sensitivity = 88.5%). RT-QuIC negative patients were younger (median = 52.0 years vs. 66.1 years, p < 0.001). Other demographic and presenting features, and CSF cell count, protein, and glucose levels were similar in RT-QuIC negative and positive patients. Frequency of 14-3-3 positivity (4/13 vs. 77/94, p < 0.001) and median CSF total tau levels were lower in RT-QuIC negative patients (2517 vs. 4001 pg/mL, p = 0.020), and time from symptom onset to first presentation (153 vs. 47 days, p = 0.001) and symptomatic duration (710 vs. 148 days, p = 0.001) were longer.
Conclusions:
RT-QuIC is a sensitive yet imperfect measure necessitating incorporation of other test results when evaluating patients with suspected prion disease. Patients with negative RT-QuIC had lower markers of neuronal damage (CSF total tau and protein 14-3-3) and longer symptomatic duration of disease, suggesting that false negative RT-QuIC testing associates with a more indolent course.
Insights
Real-time quaking-induced conversion (RT-QuIC) assays can yield false negatives in prion disease diagnosis. Patients with negative RT-QuIC results often present with younger age and a more indolent disease course.
Area of Science:
- Neurology
- Biochemistry
- Pathology
Background:
- Real-time quaking-induced conversion (RT-QuIC) assays are sensitive and specific for prion detection.
- False negative results in RT-QuIC assays are a recognized challenge in clinical prion disease diagnosis.
Purpose of the Study:
- To profile clinical, laboratory, and pathologic features associated with false negative RT-QuIC assays.
- To inform the diagnostic approach for patients with suspected prion disease.
Main Methods:
- 113 patients with probable or definite prion disease were assessed.
- Cerebrospinal fluid (CSF) RT-QuIC testing was performed.
- Clinical, laboratory, and pathologic data were collected and analyzed.
Main Results:
- 13 out of 113 patients (11.5%) had initial negative RT-QuIC results (sensitivity 88.5%).
- RT-QuIC negative patients were younger (median 52.0 vs. 66.1 years) and had longer symptomatic duration (710 vs. 148 days).
- Lower CSF 14-3-3 positivity and total tau levels were observed in RT-QuIC negative patients.
Conclusions:
- RT-QuIC is a sensitive but imperfect diagnostic tool for prion disease.
- False negative RT-QuIC results are associated with a more indolent disease course and lower markers of neuronal damage.
- Diagnostic strategies for suspected prion disease should incorporate RT-QuIC results with other clinical and laboratory findings.
