基于^(18)F-APN-1607 PET显像的阿尔茨海默病tau蛋白脑网络及偏侧性研究  

Study on tau brain network and asymmetry of Alzheimer′s disease based on ^(18)F-APN-1607 PET imaging

作　　者：王敏[1] 鲁佳荧 李玲 鲍伟奇 李明 赵倩华 左传涛 蒋皆恢[1] 管一晖 Wang Min;Lu Jiaying;Li Ling;Bao Weiqi;Li Ming;Zhao Qianhua;Zuo Chuantao;Jiang Jiehui;Guan Yihui(Shanghai Institute of Advanced Communication and Data Science,Shanghai University,Shanghai 200444,China;PET Center,Huashan Hospital,Fudan University,Shanghai 200235,China;Department of Neurology,Huashan Hospital,Fudan University,Shanghai 200040,China)

机构地区：[1]上海大学先进通信与数据科学研究院,200444 [2]复旦大学附属华山医院PET中心,上海200235 [3]复旦大学附属华山医院神经内科,上海200040

出　　处：《中华核医学与分子影像杂志》2021年第1期28-34,共7页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家自然科学基金(61603236,81971641,81271516)。

摘　　要：目的基于^(18)F-APN-1607 PET脑显像结合图论方法,揭示阿尔茨海默病(AD)患者脑内tau蛋白网络拓扑结构异常,并探讨AD患者tau蛋白沉积在左右脑组织的偏侧性。方法该横断面研究纳入2018年11月至2020年1月于复旦大学附属华山医院进行^(18)F-APN-1607 PET显像、临床确诊的23例AD患者[男9例,女14例;年龄(61.3±10.7)岁]和13名正常对照者(NC)[男9名,女4名;年龄(61.6±4.5)岁]。使用基于图论的脑网络分析方法构建NC组和AD组的tau蛋白脑网络,计算网络属性(集聚系数、最短路径长度、局部效率及小世界系数等),并获得AD组不对称系数(AI)评估tau蛋白沉积的偏侧性。使用1000次置换检验对组间脑网络参数差异进行分析。结果NC组和AD组的脑连接存在较大差异,AD组在嗅皮质和颞叶等区域存在连接减弱,而在后扣带回、楔前叶及顶枕叶等脑区连接增强;AD组的tau蛋白脑网络存在明显的拓扑结构异常,相比于NC组,在稀疏度阈值20%~50%内,AD组的集聚系数(t值:2.28~2.69)、局部效率(t值:2.34~3.06)和小世界系数(t值:2.26~3.32)等均显著下降(均P<0.05),最短路径长度显著增加(t值:2.13~2.85,均P<0.05);AD组的tau蛋白沉积在后扣带回、上顶叶、中央旁小叶、颞上回和颞中回脑区存在显著的偏侧性,AI分别为10.5%(8.1%,13.9%)、14.1%(7.6%,20.3%)、-12.4%(-15.7%,-7.8%)、-10.8%(-15.3%,-2.1%)和-12.1%(-17.9%,-6.6%)。结论基于^(18)F-APN-1607 PET影像建立的tau蛋白网络模型或可用于分析AD患者异常的拓扑结构变化,且AD患者脑内tau蛋白沉积在后扣带回、上顶叶、中央旁小叶、颞上回和颞中回脑区具有明显的偏侧性。Objective To reveal the abnormal topology of brain network in Alzheimer′s disease(AD),and evaluate the laterality of tau protein deposition in brains of AD patients based on ^(18)F-APN-1607 PET brain imaging combined with graph theory.Methods From November 2018 to January 2020,23 clinically diagnosed AD patients(9 males,14 females;age(61.3±10.7)years)and 13 normal controls(NC)(9 males,4 females;age(61.6±4.5)years)who underwent ^(18)F-APN-1607 PET imaging in Huashan Hospital,Fudan University were analyzed in this cross-sectional study.The brain network analysis method based on graph theory was used to construct the tau network of the NC group and the AD group,the network attributes(clustering coefficient,shortest path length,local efficiency,and small-worldness)were calculated,and the asymmetry index(AI)of each group to evaluate the laterality of tau protein deposition was obtained.Permutation test(1000 times)was used to analyze the differences in brain network parameters between the NC group and the AD group.Results The tau network of the AD group had obvious topological disorder,and the connections in the olfactory cortex and temporal lobe were weakened,while in the posterior cingulate gyrus,anterior wedge,and parietal occipital lobe,the connections were enhanced.Compared with NC group,clustering coefficient(t values:2.28-2.69),local efficiency(t values:2.34-3.06)and small-worldness(t values:2.26-3.32)were significantly decreased in AD group(all P<0.05)with the sparsity of 20%-50%,while the shortest path length was significantly increased(t values:2.13-2.85;all P<0.05).There was significant tau laterality in the posterior cingulate gyrus,superior parietal gyrus,paracentral lobule,superior temporal gyrus and middle temporal gyrus(AI:10.5%(8.1%,13.9%),14.1%(7.6%,20.3%),-12.4%(-15.7%,-7.8%),-10.8%(-15.3%,-2.1%),-12.1%(-17.9%,-6.6%),respectively).Conclusion The tau network analysis based on ^(18)F-APN-1607 may be used to reveal abnormal topological changes of AD patients,and the tau deposition in the posterior c

关 键 词：阿尔茨海默病 TAU蛋白质类 苯并噻唑类 正电子发射断层显像术 

分 类 号：R749.16[医药卫生—神经病学与精神病学]