Biological Fluid Biomarkers in Human Prion Diseases with a Note on Biosafety

Area of Science:

• Neurology
• Biochemistry
• Diagnostic Medicine

Background:

• Definitive diagnosis of human prion diseases (e.g., Creutzfeldt-Jakob disease) is currently postmortem.
• Premortem diagnosis relies on prion-specific assays and surrogate biomarkers, but their accuracy varies.
• Prion protein (PrP) detection and analysis are crucial for diagnosis.

Purpose of the Study:

• To review current diagnostic methods for human prion diseases.
• To evaluate the utility of various biomarkers in cerebrospinal fluid (CSF) and blood.
• To highlight the importance of biosafety in handling samples.

Main Methods:

• Review of postmortem diagnostic criteria including neuropathology and genetic studies.
• Analysis of premortem diagnostic assays: protein misfolded cyclic amplification (PMCA) and real-time quaking-induced conversion (RT-QuIC).
• Assessment of surrogate biomarkers in CSF (e.g., 14-3-3, tau, NfL) and blood for diagnostic and prognostic value.

Main Results:

• Postmortem diagnosis combines clinical, neuropathological, and molecular findings.
• RT-QuIC and PMCA in CSF show promise for premortem diagnosis.
• CSF biomarkers like 14-3-3 and tau have variable sensitivity/specificity; NfL and others require further validation.
• Blood biomarkers have limited diagnostic value, though tau and NfL may track progression.

Conclusions:

• Accurate diagnosis of prion diseases requires a multi-faceted approach.
• Prion-specific assays in CSF are key for premortem diagnosis.
• Careful sample handling and biosafety are essential due to infectious agents.