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Creutzfeldt-Jakob disease: blood infectivity and screening tests
1Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4122, USA.
Abstract:
Blood infectivity data from rodent models of transmissible spongiform encephalopathies (TSEs), and infectivity-prion protein (PrP) equivalence data from scrapie-infected hamster brain suggest a minimum requirement for PrP detection in blood buffy coat of < or = 10 pg/mL. This estimate could either be more or less stringent than calculated-more, if infectivity levels in human blood are lower than in experimental rodent models; less, if the infectivity-PrP ratio is lower in blood than in brain tissue, or if there is a large as yet undetected pool of abnormal but proteinase-sensitive PrP. None of several testing methods under development has yet achieved the calculated sensitivity requirement, but a few are within range, and it should be possible within the coming year to determine whether PrP occurs at a practically detectable level in the blood of patients with TSE.
Insights
Detecting prion protein (PrP) in blood is crucial for diagnosing transmissible spongiform encephalopathies (TSEs). Current methods aim for a sensitivity of 10 pg/mL, with ongoing research to confirm PrP detectability in patient blood.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases.
- Prion protein (PrP) is the key pathological marker in TSEs.
- Detecting PrP in blood could enable early diagnosis.
Purpose of the Study:
- To estimate the minimum detectable level of PrP in blood for TSE diagnosis.
- To assess the feasibility of current testing methods for blood PrP detection.
Main Methods:
- Analysis of blood infectivity data from rodent TSE models.
- Evaluation of infectivity-prion protein equivalence from hamster scrapie models.
- Review of ongoing development of sensitive PrP detection assays.
Main Results:
- A minimum requirement for PrP detection in blood buffy coat is estimated at <= 10 pg/mL.
- This sensitivity threshold may vary based on infectivity levels and PrP characteristics in human blood compared to animal models.
- No current testing method has yet achieved this calculated sensitivity, but some are approaching it.
Conclusions:
- Further development is needed to achieve the required sensitivity for blood PrP detection.
- Ongoing research aims to determine if PrP is detectable in the blood of TSE patients within the next year.