Developments in diagnosis for prion diseases

The protease resistant isoform of prion protein (PrP) is a diagnostic marker of spongiform encephalopathies in humans and animals. Immunoblotting is a sensitive method but requires either fresh or frozen, unfixed materials. Immunohistochemistry using formalin-fixed, paraffin-embedded materials is now also considered to be sensitive and comparable to immunoblotting after various treatments, especially using the hydrolytic autoclaving method on tissue sections before staining. The advantage of this method is that it can be applied to routine pathology materials or long preserved materials. The kuru plaque-type deposition of PrP suggests abnormalities of the PrP gene, while synaptic-type deposition suggests either sporadic CJD or particular familial CJD. PrP gene abnormalities are thus related to PrP deposition and modify clinical symptoms and their progression. A PrP gene analysis can be done using either preclinical, clinical or post-mortem materials. A protease resistant isoform (PrPCJD, PrPSc) of the prion protein (PrP) has been exclusively detected in humans and animals with spongiform encephalopathies. Human and laboratory animal brains with either no disease or other diseases have never shown PrPC^0, while those with Pi-pCJD have often transmitted spongiform encephalopathies to labora-tory animals, especially to mice in our laboratory. A cellular isoform (PrPC) of the protein exists in normal cells, and can be eliminated by protease digestion and does not disturb the detection of PrP^D in our diagnostic procedures. at Pennsylvania State U niversity on February 20, 201