Histopathology and immunohistochemistry of human transmissible spongiform encephalopathies (TSEs)

Neuropathological examination has remained the most important tool to give a definite diagnosis of human transmissible spongiform encephalopathies (TSEs). In recent years, immunohistochemistry (IHC) for the disease-associated prion protein (PrP) has emerged as an indispensable adjunct to the neuropathological confirmation of TSEs, especially in cases with equivocal histopathological changes. The clinico-pathological phenotype including histopathology and IHC for PrP depends upon PrPres fragment size and codon 129 genotype in the PrP gene, PRNP. However, some TSEs have little or no spongiform change or detectable PrP, such as fatal familial insomnia (FFI). IHC for PrP requires appropriate technique, has some pitfalls and thus should be interpreted by experienced observers. The amount and distribution of PrP deposits do not always correlate with type and severity of local tissue damage. PrP deposition occurs only where neuronal parenchyma is present; in pre-existing tissue lesions such as scarred infarctions with prominent gliosis, PrP does not accumulate. Most recently, new patterns of granular ganglionic and tiny adaxonal PrP deposits were described in the peripheral nervous system in rare human TSE cases and experimental scrapie. There is early, severe and selective loss of a peculiar parvalbumin-expressing subset of inhibitory GABAergic neurons both in human and experimental TSEs.