| Abstract: | Recent work has shown that frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) is caused by tau gene mutations. Several different exonic and intronic mutations in the tau gene heve been found in many families with FTDP-17. Patients with tau gene mutations show a wide variety of clinicopathological conditions, such as frontotemporal dementia, corticobasal degeneration, multiple system tauopathy with presenile dementia, pallido-ponto-nigral degeneration, disinhibition-dementia-parkinsonism-amyotrophy complex, and progressive sub-cortical gliosis. A Japanese family of frontotemporal dementia with a missense mutation S305N in exon 10 of the tau gene is reported. Post-mortem examination of the brain revealed ring-shaped neurofibrillary tangles (NFT) partially surrounding the nucleus, which were most prominent in the frontal, temporal, insular, and postcentral cortices, as well as in the dentate gyrus. Cortical NFT were restricted primarily to layer II. The missense mutation S305N did not reduce the ability of tau to promote microtubule assembly. Instead, it increased splicing of exon 10. Weak immunoreactivities of kinases for tau phosphorylation were found in late-stage NFT in the dentate gyrus, whereas strong immunoreactivities were seen in early stage NFT in the temporal cortex. PP2B was present in temporal NFT. Although anti-PP2A antibody labeled neurons, NFT were not stained, which suggests that the activity of this phosphatase might be decreased in NFT. |
