Defining the limits of prion disease

The term prion disease applies to any disease in which there is an accumulation in brain of the abnormal isoform of prion protein, known as PrP^sc. These diseases include all the transmissible spongiform encephalopathies of humans and animals and their related atypical forms. Although there are clear clinical and neuropathological indicators in the majority of cases, the atypical forms present particular diagnostic difficulties because their clinical presentation may closely resemble much more common forms of dementia. On pathological examination the brain may show no spongiform encephalopathy, and attempts at transmission are often not successful in these cases. There are various biochemical and immunohistochemical ways in which prion disease can be detected. Some of these require the use of fresh/frozen tissue which is often not available unless prion disease is already suspected. Some previously unsuspected cases have been detected by genetic analysis of the PrP gene. This approach must be used with caution since there are several rare polymorphisms in the PrP gene which are not pathogenic and possession of a pathogenic mutation does not prevent the occurrence of more common neurological disorders at an earlier age, some of which may be treatable.