第48回日本神経学会総会
＜シンポジウム7-3＞認知症「治療を展望したAlzheimer病の早期診断―MCIから初期Alzheimer病へ」
リスクファクターとしての遺伝子
桑野 良三
新潟大学脳研究所附属生命科学リソース研究センターバイオリソース研究部門〔〒951-8585 新潟市中央区旭町通り1-757〕
The Japanese Genetic Study Consortium for Alzheimer's disease (JGSCAD) was organized in 2000 to discover strategies to delay onset and progression of dementia. To identify an additional gene (s) causing susceptibility to APOE-ε4 negative late-onset AD (LOAD), we performed single nucleotide polymorphisms (SNP)-based association analysis on chromosomes 10 with only the APOE-ε3*3 genotype. The significant associated SNPs, spanning 220 kb at genomic position 101 Mb, with LOAD and were located in the dynamin-binding protein (DNMBP) gene. Quantitative real-time RT-PCR analysis demonstrated that neuropathologically confirmed LOAD brains exhibit a significant reduction of DNMBP mRNA compared with age-matched ones. DNMBP was discovered as a scaffold protein that brings the dynamin and actin regulatory proteins together, and is concentrated at synapses. In view of the fact that synaptic dysfunction precedes Aβ deposition in the brains of AD patients, our observations raise the possibility that DNMBP, as one of risk factors, might play a predominant role in the early stage of LOAD lacking the APOE-ε4 allele. Novel genetic risk factors will be discovered through genome-wide association studies with high density of SNP markers.
(臨床神経, 47：908−911, 2007)
key words：アポリポプロテインE, 遺伝的リスクファクター, ダイナミン結合タンパク, ゲノム網羅的相関解析
（受付日：2007年5月16日）
