DEMENTIA ASSOCIATED WITH A 216 BASE-PAIR INSERTION IN THE PRION PROTEIN GENE - CLINICAL AND NEUROPATHOLOGICAL FEATURES

We report the clinical and neuropathological findings in a patient with a 216 base pair insertion in the prion protein (PrP) gene. She died aged 57 years after a 2.5-year illness characterized by falls, axial rigidity, myoclonic jerks and progressive dementia. There was no history of affected relatives. The pathological changes consisted of the deposition in cerebellum, basal ganglia and cortex of small plaques composed of variable amounts of amyloid and degenerative material which was associated with a marked macrophage reaction. The amyloid deposits in the cerebellum and basal ganglia gave a positive immunoperoxidase staining reaction for PrP. In some places plaques bore a resemblance to senile neuritic plaques and in the hippocampus there were abundant typical neuritic plaques giving positive staining reactions for beta-amyloid protein and tau protein, but not PrP. There were few neurons bearing neurofibrillary tangles. This is the first report of the neuropathological changes associated with this particular abnormality of the PrP gene and it seems to demonstrate a transition between the pathology of prion disease and that of Alzheimer's disease. The importance of PrP gene analysis to the understanding of neurodegenerative diseases is stressed.