FAMILIAL GERSTMANN-STRAUSSLER-SCHEINKER DISEASE WITH NEUROFIBRILLARY TANGLES

Patients affected with Gerstmann-Straussler-Scheinker disease from two families, one from Indiana and one of Swedish origin, have been studi ed. The patients are clinically characterized by cerebellar ataxia, ex trapyramidal signs, and dementia. Accumulation of amyloid deposits and neurofibrillary tangles are the most conspicuous neuropathologic feat ures. In the patients from the Indiana family, the amyloid contains an 11-kDa peptide, an amyloidogenic degradation product of the prion pro tein. The neurofibrillary tangles are composed of paired helical filam ents and immunoreact with antibody to A68, an abnormally phosphorylate d form of the microtubule-associated protein tau. In these families, t he disease is caused by a point mutation in the PRNP gene. In the Indi ana family, the mutation is at codon 198, and in the Swedish family at codon 217.