NEUROFIBRILLARY TANGLES IN GERSTMANN-STRAUSSLER-SCHEINKER-SYNDROME WITH THE A117V PRION GENE MUTATION

One patient of a French family with Gerstmann-Straussler-Scheinker syn drome with the mutation in codon 117 of the prion protein (PrP) gene d isplayed unexpected neuritic degeneration around PrP plaques and numer ous diffuse neurofibrillary tangles, whereas other members did not. Th e tau profile in this patient's brain was analysed and compared with o ne from another member of the Gerstmann-Straussler-Scheinker family as well as with the Alzheimer's tau profile. A panel of well characteris ed antibodies against both normal tau protein and paired helical filam ents-tan protein was used on immunoblots of brain proteins resolved by mono and two dimensional gels. The tau profile in the patient with Ge rstmann-Straussler-Scheinker syndrome without neurofibrillary tangles was normal. The tau profile from the patient with Gerstmann-Straussler -Scheinker syndrome and neurofibrillary tangles was characterised by a hyperaggregation state of tau protein. This case illustrates the phen otypic heterogeneity of the GSS117 mutation not only from one family t o another, but also between members of the same family. In this family , the presence of neurofibrillary tangles is still unexplained, but co uld be correlated with either the protracted duration of the disease o r the old age of the patient.