FAMILIAL MULTIPLE-SYSTEM TAUOPATHY WITH PRESENILE-DEMENTIA IS LOCALIZED TO CHROMOSOME-17

An autosomal dominant presenile dementia affecting 39 individuals in a seven-generation, 383-member pedigree has been studied at Indiana Uni versity. In the affected members of this family, clinical symptoms occ urred early in life, with an average age at onset of 48.8 years. The p resenting clinical features include disequilibrium, neck stiffness, dy sphagia, and memory loss. As the disease progresses, further cognitive decline, superior-gaze palsy, and dystaxia also are observed. The ave rage duration from onset of symptoms to death is similar to 10 years. Neuropathologic studies of nine affected individuals showed neuronal l oss in several areas of the CNS, as well as argentophilic tau-immunopo sitive inclusions in neurons and in oligodendroglia. A limited genomic screen by use of DNA samples from 28 family members localized the gen e for this disorder to a 3-cM region on chromosome 17, between the mar kers THRA1 and D17S791. The gene for tau also was analyzed, through sa mples from the family.