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Preclinical Detection of Prions in Blood of Nonhuman Primates Infected with Variant Creutzfeldt-Jakob Disease
Abstract:
Variant Creutzfeldt-Jakob disease (vCJD) is caused by prion infection with bovine spongiform encephalopathy and can be transmitted by blood transfusion. Protein misfolding cyclic amplification (PMCA) can detect prions in blood from vCJD patients with 100% sensitivity and specificity. To determine whether PMCA enables prion detection in blood during the preclinical stage of infection, we performed a blind study using blood samples longitudinally collected from 28 control macaques and 3 macaques peripherally infected with vCJD. Our results demonstrate that PMCA consistently detected prions in blood during the entire preclinical stage in all infected macaques, without false positives from noninfected animals, when using the optimized conditions for amplification of macaque prions. Strikingly, prions were detected as early as 2 months postinoculation (>750 days before disease onset). These findings suggest that PMCA has the potential to detect vCJD prions in blood from asymptomatic carriers during the preclinical phase of the disease.
Insights
Protein misfolding cyclic amplification (PMCA) can detect variant Creutzfeldt-Jakob disease (vCJD) prions in blood during the preclinical stage. This method shows potential for early detection in asymptomatic carriers.
Area of Science:
- Neuroscience
- Infectious Diseases
- Biochemistry
Background:
- Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder linked to prion infection.
- Bovine spongiform encephalopathy (BSE) is the causative agent, with transmission occurring via blood transfusion.
- Early detection of vCJD prions is crucial for preventing disease spread.
Purpose of the Study:
- To evaluate the efficacy of Protein Misfolding Cyclic Amplification (PMCA) for detecting vCJD prions in blood during the preclinical infection stage.
- To assess PMCA's sensitivity and specificity in a longitudinal animal model.
- To determine the earliest point at which vCJD prions can be detected in blood.
Main Methods:
- A blind study was conducted using blood samples from 28 control macaques and 3 macaques peripherally infected with vCJD.
- Longitudinal blood samples were analyzed using optimized PMCA conditions for macaque prions.
- Prion detection was performed without knowledge of sample status (control or infected).
Main Results:
- PMCA consistently detected vCJD prions in the blood of all infected macaques throughout the preclinical stage.
- No false positives were observed in blood samples from control, non-infected macaques.
- Prions were detected as early as 2 months post-inoculation, over 750 days before disease onset.
Conclusions:
- PMCA demonstrates high sensitivity and specificity for detecting vCJD prions in blood during the preclinical phase.
- The technique enables detection of vCJD prions in asymptomatic individuals.
- PMCA holds significant potential for early diagnosis and surveillance of vCJD through blood screening.

