首页|基于11C-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

基于11C-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 A β deposition and functional connectivity changes in patients with Alzheimer's disease based on 11C-PIB PET/MR

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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APOE ε4+23例[男12例、女11例,年龄(74.8±8.4)岁]、APOE ε4-20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11C-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APOE ε4+和APOE ε4-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APOE ε4+基因携带者组,APOE ε4+与APOE ε4-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).APOE ε4+和APOE ε4-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,APOE ε4+、APOE ε4-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,APOE ε4+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APOE ε4-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 on β-amy-loid(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 APOE ε4+patients(12 males and 11 females,age(74.8±8.4)years),20 APOE ε4-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 11C-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 Aβ deposition between APOE ε4+patients and APOE ε4-patients,and the correlation between subcortical structure and brain FC.Results The GMV of bilateral amygdala between NC group and APOE ε4+gene carrier group,and between APOE ε4+and APOE ε4-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 APOE ε4+and APOE ε4-gene carrier groups,with a more pronounced effect observed in the APOE ε4+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 con-nectivity map among APOE ε4+,APOE ε4-carriers and NC groups.With the amygdala as the seed point,the whole brain connectivity in the APOE ε4+gene carrier group was significantly reduced,and the connectivity between the amygdala and the cingulate gyrus,parietal lobe and temporal lobe was significantly reduced in the APOE ε4+gene carrier group compared with NC group,while the connectivity between the amygdala and the whole brain was not significantly reduced in the APOE ε4-gene carrier group.Aβ deposition in amygdala was positively correlated with FC coefficients of frontal brain regions,gyrus rectus,right middle occipital gyrus and left temporal lobe(r values:0.56-0.70,all P<0.05).Conclusion APOE influences GMV and Aβdeposition of hippocampus and amygdala,and FC of amygdala,and may be involved in the pathological mechanism of cognitive impairment.

Alzheimer diseaseAmyloid beta-peptidesApolipoproteins EThiazolesPositron-emission tomographyMagnetic resonance imaging

常燕、张熙琬、吴世娜、刘家金、付华平、张锦明、刘若卓、单保慈、王瑞民

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解放军总医院第一医学中心神经内科,北京 100853

北京理工大学光电学院,北京 100081

解放军总医院第一医学中心核医学科,北京 100853

中国科学院高能物理研究所核技术应用研究中心,北京 100049

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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

国家自然科学基金国家重点研发计划科技创新2030重大项目

823719992022YFC20099052021ZD0201804

2024

中华核医学与分子影像杂志
中华医学会

中华核医学与分子影像杂志

CSTPCD北大核心
影响因子:1.107
ISSN:2095-2848
年,卷(期):2024.44(5)
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