Late‐onset frontotemporal dementia with a novel exon 1 (Arg5His) tau gene mutation

Abstract We report a case of frontotemporal dementia and parkinsonism linked to chromosome 17 of 5 years' duration in an 81‐year‐old man whose brother had died at age 86 years with dementia. In this patient, we found frontal and temporal neuronal loss, glial‐predominant tau deposits, progressive supranuclear palsy‐like straight tubules, accumulation of 4‐repeat‐predominant Sarkosyl‐insoluble tau, and a novel exon 1 (Arg5His) tau gene mutation. This mutation decreased microtubule‐promoting capacity and increased fibrillation of tau in vitro. Thus, we consider that the Arg5His mutation is an authentic tau gene abnormality responsible for the patient's tau pathology and late‐onset dementia.