Phenotypic variability in the brains of a family with a prion disease characterized by a 144-base pair insertion in the prion protein gene.

The use of prion protein (PrP) immunohistochemistry in neuropathology has allowed identification of prion diseases with otherwise atypical histological features. The brains from family members with familial prion diseases can show marked histological variation. A histological and immunohistochemical study was performed on 10 brains of patients with a familial prion disease caused by a 144-base pair (bp) insertion in the prion protein gene. The histology from the cases showed variability in the severity of spongiform change and astrocytosis in both the cerebellum and the cerebrum. There was also variability in the density of microglial cells. The PrP immunohistochemistry revealed that in nine cases there was a similar patch-like deposition of PrP within the molecular layer of the cerebellum. Although in the cerebellum there did seem to be some correlation between the severity of spongiform change, astrocytosis and the density of microglial cells, there was no such correlation between any of these three parameters and the density of PrP staining. There was deposition of beta-amyloid precursor protein (beta-APP) in the cerebellum, suggesting that disrupted axonal transport had a possible role in the evolution of the disease. The cases illustrate the histological variability that can occur in familial prion diseases despite similarity in PrP staining. They also reveal that the relationship between PrP deposition and cerebral or cerebellar damage might be complex.