A distinct familial presenile dementia with a novel missense mutation in the tau gene

WE report a Japanese family with early onset hereditary frontotemporal deme ntia and a novel missense mutation (Ser305Asn) in the tau gene. The patient s presented with personality changes followed by impaired cognition and mem ory as well as disorientation, but minimal Parkinsonism. Imaging studies sh owed fronto-temporal atrophy with ventricular dilatation more on the left, and postmortem examination of the brain revealed numerous neurofibrillary t angles (NFTs) with an unusual morphology and distribution. Silver-stained s ections showed ring-shaped NFTs partially surrounding the nucleus that were most prominent in frontal, temporal, insular and postcentral cortices, as well as in dentate gyrus. Cortical NFTs were restricted primarily to layer II, and were composed of straight tubules, Numerous glial cells containing coiled bodies and abundant neuropil threads were detected in cerebral white matter, hippocampus, basal ganglia, diencephalon and brain stem, but no se nile plaques or other diagnostic lesions were seen. Both the glial and neur onal tangles were stained by antibodies to phosphorylation-independent and phosphorylation-dependent epitopes in tau, Thus, this novel mutation causes a distinct familial tauopathy. (C) 1999 Lippincott Williams & Wilkins.