This mutation was found in five GSS families, all from Japan. The disease manifests itself as spastic paraparesis with brisk reflexes and the presence of the Babinski sign; in the terminal stages a patient becomes tetraplegic and demented with extrapyramidal signs (tremor and limb rigidity). The illness starts at around 40– –50 years of age and has a long course of 6–12 years. PrP deposits are encountered mainly in the cerebral cortex and, less frequently, in the striatum. The cerebellum is affected only minimally. In two cases, sparse neurofibrillary tangles (NFT) composed of paired helical filaments (PHF) were seen. Numerous NFT were found in the case of 57-year-old female with dementia but not spastic paraparesis. It is noteworthy that in a case described by Amano et al. plaques of an-other type were seen, localized in the 5th and 6th layers of the cerebral cortex, weakly PAS-positive, confluent and of laminar distribution.