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

弥漫性钙化性神经元缠结（Diffuse neuroendocrystallization with calcification，DNTC）患者脑内小胶质细胞活化机制及ApoE/tau基因分析弥漫性钙化性神经元缠结（Diffuse neuroendocrystallization with calcification，DNTC）是一种不典型的痴呆，其病理特征为弥漫性神经元缠结（diffuse neuroendocrystallization，NFT），无老年斑（senile plaque，SP）。在这项研究中，我们调查了人类白细胞抗原（HLA）-DR阳性激活的小胶质细胞在6例DNTC和6例阿尔茨海默病（AD）患者的死后脑组织中的分布。HLA-DR阳性的活化小胶质细胞在AD中与SP相关。在缺乏SP的DNTC脑中，HLA-DR阳性小胶质细胞主要聚集在弱tau阳性NFT周围，这些NFT也对抗淀粉样蛋白-P和抗C3 d抗体呈阳性。这项研究的结果表明，补体途径也被激活的DNTC大脑和免疫和炎症反应，包括小胶质细胞激活，可能发生在DNTC患者的细胞外NFT周围。为了进行遗传学研究，招募了6名DNTC患者。在书面知情同意书后，从外周血样品中提取DNA。使用dHPLC方法和直接测序进行突变搜索。采用PCR-RFLP和引物延伸法进行基因分型。在tau基因中发现6个SNP。其中Val 279 Met多态性与DNTC有一定的关联性，但涉及的病例较少。DNTC与ApoE基因座无相关性。

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.