| Project/Area Number |
12670962
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Fujita health university |
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Principal Investigator |
NAITOH Hiroshi Fujita Health University, School of Medicine, Associate Professor, 医学部, 助教授 (00247644)
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| Co-Investigator(Kenkyū-buntansha) |
OZAKI Norio Nagoya University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (40281480)
SAWADA Makoto Fujita Health University, Institute For Comprehensive Medical Science, Professor, 総合医科学研究所, 教授 (10187297)
IWATA Nakao Fujita Health University, School of Medicine, Professor, 医学部, 教授 (60312112)
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| Project Period (FY) |
2000 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Diffuse neurofibrillary tangles with calcification / Alzheimer disease / Microglia / HLA-DR / Neurofibrillary tangles / tau gene / Val279Met polymorphism / タウ蛋白 / アポプロテインE遺伝子 / 遺伝子多型 / アポリポプロテインE遺伝子 / DNTC / presenile dementia / neurofibrillary tangle / microglia / inflammation |
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| Research Abstract |
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.
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