title: A distinct familial presenile dementia with a novel missense mutation in the tau gene.
abstract: We report a Japanese family with early onset hereditary frontotemporal dementia and a novel missense mutation (Ser305Asn) in the tau gene. The patients presented with personality changes followed by impaired cognition and memory as well as disorientation, but minimal Parkinsonism. Imaging studies showed fronto-temporal atrophy with ventricular dilatation more on the left, and postmortem examination of the brain revealed numerous neurofibrillary tangles (NFTs) with an unusual morphology and distribution. Silver-stained sections 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 senile plaques or other diagnostic lesions were seen. Both the glial and neuronal tangles were stained by antibodies to phosphorylation-independent and phosphorylation-dependent epitopes in tau. Thus, this novel mutation causes a distinct familial tauopathy.
authors: Department of Neuropsychiatry, Shimane Medical University, Izumo, Japan.
authors: M
authors: M
authors: Iijima
authors: T
authors: T
authors: Tabira
authors: P
authors: P
authors: Poorkaj
authors: G D
authors: GD
authors: Schellenberg
authors: J Q
authors: JQ
authors: Trojanowski
authors: V M
authors: VM
authors: Lee
authors: M L
authors: ML
authors: Schmidt
authors: K
authors: K
authors: Takahashi
authors: T
authors: T
authors: Nabika
authors: T
authors: T
authors: Matsumoto
authors: Y
authors: Y
authors: Yamashita
authors: S
authors: S
authors: Yoshioka
authors: H
authors: H
authors: Ishino
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence / Q000235:genetics; D001284:Atrophy; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003704:Dementia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D016875:tau Proteins