基于^(11)C-PIB PET/MR研究APOE对阿尔茨海默病患者皮质下结构Aβ沉积和功能连接改变的影响  

Effects of APOE on subcortical Aβdeposition and functional connectivity changes in patients with Alzheimer′s disease based on ^(11)C-PIB PET/MR

作　　者：常燕 张熙琬 吴世娜 刘家金[3] 付华平[3] 张锦明[3] 刘若卓[1] 单保慈[4] 王瑞民[3] Chang Yan;Zhang Xiwan;Wu Shina;Liu Jiajin;Fu Huaping;Zhang Jinming;Liu Ruozhuo;Shan Baoci;Wang Ruimin(Department of Neurology,the First Medical Centre,Chinese PLA General Hospital,Beijing 100853,China;School of Optics and Photonics,Beijing Institute of Technology,Beijing 100081,China;Department of Nuclear Medicine,the First Medical Centre,Chinese PLA General Hospital,Beijing 100853,China;School of Nuclear Science and Technology,University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]解放军总医院第一医学中心神经内科,北京100853 [2]北京理工大学光电学院,北京100081 [3]解放军总医院第一医学中心核医学科,北京100853 [4]中国科学院高能物理研究所核技术应用研究中心,北京100049

出　　处：《中华核医学与分子影像杂志》2024年第5期285-290,共6页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家自然科学基金(82371999);国家重点研发计划(2022YFC2009905);科技创新2030-重大项目(2021ZD0201804)。

摘　　要：目的探讨阿尔茨海默病(AD)患者载脂蛋白E(APOE)ε4等位基因对皮质下结构的β-淀粉样蛋白(Aβ)沉积、脑区之间的功能连接(FC)的影响。方法前瞻性纳入2023年1月至2023年10月间解放军总医院第一医学中心临床诊断为很可能的轻/中度AD患者43例,包括APOEε4+23例[男12例、女11例,年龄(74.8±8.4)岁]、APOEε4-20例[男14例、女6例,年龄(77.6±8.9)岁],以及认知功能正常受试者(NC)20名[男15名、女5名,年龄(75.3±6.2)岁]。所有受试者行^(11)C-匹兹堡化合物B(PIB)PET/MR脑显像。使用单因素方差分析、最小显著差异t检验比较3组受试者间皮质下结构(海马、杏仁核)的灰质体积(GMV)差异;采用两独立样本t检验比较APOEε4+和APOEε4-基因携带者组间Aβ沉积差异;采用Pearson相关分析ROI Aβ沉积与各脑区FC系数的相关性。结果NC组与APOEε4+基因携带者组,APOEε4+与APOEε4-基因携带者组双侧杏仁核GMV差异有统计学意义(F=6.43,P=0.002;P值:0.002、0.003);3组间双侧海马GMV差异有统计学意义(F=5.34,P=0.030)。APOEε4+和APOEε4-基因携带者组间海马和杏仁核均存在PIB异常摄取,APOEε4+组摄取更高(t值:3.14、2.19,P值:0.032、0.009)。以海马为种子点,APOEε4+、APOEε4-基因携带者及NC组的全脑连接图无明显异常。以杏仁核为种子点,APOEε4+基因携带者组全脑连接可见强度明显减弱,其在扣带回、顶叶和颞叶等脑区较NC组明显降低;而APOEε4-基因携带者组杏仁核与全脑连接强度无明显降低脑区。杏仁核Aβ沉积和杏仁核与额叶多个脑区、回直肌、右侧枕中回及左侧颞叶FC系数均呈正相关(r值:0.56~0.70,均P<0.05)。结论APOE基因型影响海马、杏仁核GMV和Aβ沉积以及杏仁核FC,并可能参与了认知功能损害的病理机制。Objective To investigate the effects of apolipoprotein E(APOE)ε4 allele onβ-amyloid(Aβ)deposition in subcortical structures and functional connectivity(FC)between brain regions in patients with Alzheimer′s disease(AD).Methods Forty-three patients with probable mild/moderate AD were prospectively enrolled from the First Medical Centre,Chinese PLA General Hospital between January 2023 and October 2023,including 23 APOEε4+patients(12 males and 11 females,age(74.8±8.4)years),20 APOEε4-patients(14 males and 6 females,age(77.6±8.9)years)and 20 normal cognitive volunteers(NC)(15 males and 5 females,age(75.3±6.2)years).All subjects underwent^(11)C-Pittsburgh compound B(PIB)PET/MR brain imaging.The differences of gray matter volume(GMV)in subcortical structures(hippocampus,amygdala)among the three groups were analyzed by one-way analysis of variance and least significant difference(LSD)t test.Independent-sample t test and Pearson correlation analysis were used to analyze difference in Aβdeposition between APOEε4+patients and APOEε4-patients,and the correlation between subcortical structure and brain FC.Results The GMV of bilateral amygdala between NC group and APOEε4+gene carrier group,and between APOEε4+and APOEε4-gene carrier groups were significantly different(F=6.43,P=0.002;P values:0.002,0.003).Significant difference of GMV was observed in the bilateral hippocampus among three groups(F=5.34,P=0.030).Abnormal PIB uptake was detected in both the hippocampus and amygdala of both APOEε4+and APOEε4-gene carrier groups,with a more pronounced effect observed in the APOEε4+group(t values:3.14,2.19,P values:0.032,0.009).Taking the hippocampus as the seed point,there was no obvious abnormality in the whole brain connectivity map among APOEε4+,APOEε4-carriers and NC groups.With the amygdala as the seed point,the whole brain connectivity in the APOEε4+gene carrier group was significantly reduced,and the connectivity between the amygdala and the cingulate gyrus,parietal lobe and temporal lobe was significant

关 键 词：阿尔茨海默病 淀粉样β肽类 载脂蛋白E类 噻唑类 正电子发射断层显像术 磁共振成像 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R816.1[医药卫生—临床医学]