Study on activation mechanism of brain microglia and gentic analysis of ApoE/tau gene in patients with diffuse neurofibriliary tangles with calcification (DNTC)

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Study on Activation mechanism of brain microglia and gentic analysis of ApoE/tau gene in patients with diffuse neurofibrillary tangles with calcification (DNTC)Diffuse neurofibrillary tangles with calcification (DNTC) is an atypical dementia and is characterized pathologically by diffuse neurofibrillary tangles (NFTs) without senile plaques (SPs). In this study, we investigated the distribution of human leukocyte antigen (HLA)-DR-positive activated microglia in postmortem brain tissue of six patients with DNTC and six patients with Alzheimer disease (AD). HLA-DR-positive activated microglia were observed to associate with SPs in AD. In the DNTC brain, which lacks SPs, HLA-DR-positive microglia were mainly accumulated around weakly tau-positive NFT's, which were also positive for anti-amyloid-P and anti-C3d antibodies. The results of this study suggest that the complement pathway is also activated in the DNTC brain and that immune and inflammatory responses, including microglia activation, may occur around extracellular NFTs in DNTC patients. For genetic study, 6 DNTC patients were recruited. After written informed consent, DNA were extracted from peripheral blood samples. Mutation search were performed using dHPLC methods and direct sequencing. PCR-RFLP and primer extension were done for genotyping. In tau gene, 6 SNPs were identified. Among them, Val279Met polymorphism showed a tendent association with DNTC, however the number of patients is too small. There is no association between DNTC and ApoE locus.