阿尔茨海默病患者海马亚区体积与脑脊液生物标志物的相关性研究  

orrelations of hippocampal subfield volumes with cerebrospinal fluid biomarkers in patients with Alzheimer's disease

作　　者：朱正阳 龚乘丙 秦若梦 宋文婷 赵辉[1] 徐运[1] Zhu Zhengyang;Gong Chengbing;Qin Ruomeng;Song Wenting;Zhao Hui;Xu Yun(Department of Neurology,Drum Tower Clinical College,Nanjing University of Chinese Medicine,Nanjing 210008,China;Department of Neurology,Nanjing Drum Tower Hospital Affiliated to Medical School,Nanjing University,Nanjing 210008,China)

机构地区：[1]南京中医药大学鼓楼临床医学院神经内科,南京210008 [2]南京大学医学院附属鼓楼医院神经内科,南京210008

出　　处：《中华神经医学杂志》2023年第10期1023-1029,共7页Chinese Journal of Neuromedicine

基　　金：国家重点研发计划(2018YFC1704400)。

摘　　要：目的:探讨阿尔茨海默病(AD)患者的海马亚区体积与脑脊液(CSF)生物标志物之间的相关性。方法:选择南京中医药大学鼓楼临床医学院神经内科自2017年5月至2021年12月收治的49例认知障碍患者,其中AD患者30例,非AD患者19例。采用酶联免疫吸附试验(ELISA)分析患者CSF中Aβ1-42、总tau蛋白和磷酸化tau蛋白的浓度,使用FreeSurfer图像分析软件计算海马各个亚区体积。比较2组患者临床资料、神经心理学评分及CSF生物标志物浓度的差异,偏相关分析评估患者海马亚区体积与CSF生物标志物浓度的相关性。结果:AD组患者的简明精神状态检查量表(MMSE)评分、CSF中Aβ1-42浓度明显低于非AD组,差异均有统计学意义(P<0.05);AD组患者右侧海马的旁下托、齿状回、CA4体积明显低于非AD组,差异均有统计学意义(P<0.05)。AD组患者右侧海马旁下托体积与CSF中Aβ1-42浓度呈负相关关系(r=-0.445,P=0.023),与磷酸化tau蛋白浓度呈正相关关系(r=0.393,P=0.047);AD组患者左侧海马尾、CA1、旁下托、分子层、齿状回、CA3和CA4体积与CSF中总tau蛋白浓度均呈负相关关系(P<0.05)。非AD组患者海马亚区体积和CSF生物标志物浓度均无明显相关关系(P>0.05)。结论:与存在认知障碍的非AD患者相比,AD患者部分右侧海马亚区体积出现萎缩,其右侧海马下托在疾病发展过程中可能发挥了代偿作用。而左侧海马的多数亚区体积随着CSF中总tau蛋白浓度升高而减少。Objective To study the correlations of hippocampal subfield volumes with cerebrospinal fluid(CSF)biomarkers in Alzheimer's disease(AD)patients.Methods Forty-nine patients with cognitive impairment,including 30 AD patients and 19 non-AD patients,were recruited in Department of Neurology,Drum Tower Clinical College,Nanjing University of Chinese Medicine from May 2017 to December 2021.Concentrations of Aβ1-42,total tau protein and phosphorylated tau protein in CSF were analyzed by enzyme-linked immunosorbent assay(ELISA).Volumes of 12 hippocampal subfields were calculated using FreeSurfer image analysis.Differences of clinical data,neuropsychological scores and CSF biomarker concentrations between the 2 groups were compared.Partial correlation was performed to analyze the correlations of volumes of hippocampal subfields with CSF biomarker concentrations.Results AD patients had significantly lower Mini-mental State Examination(MMSE)scores and Aβ1-42 concentration in CSF than non-AD patients(P<0.05);AD patients had significantly lower volumes of the right hippocampal parasitulum,dentate gyrus and CA4 than non-AD group(P<0.05);the right parasubiculum volume was negatively correlated with CSF Aβ1-42(r=-0.445,P=0.023)and positively correlated with CSF P-tau(r=0.393,P=0.047)in AD patients.Volumes of left hippocampus tail,parasubiculum,CA1,molecular layer,dentate gyrus,CA3 and CA4 were negatively correlated with CSF total tau(P<0.05).No significant correlation was noted between hippocampal subfield volumes and CSF biomarker concentrations in non-AD patients.Conclusion Some right hippocampal subfields in AD patients atrophy compared with those in non-AD patients with cognitive impairment;the right parasubiculum may play a compensatory role in disease process,while volumes of the left hippocampus decreased with increased CSF total tau.

关 键 词：阿尔茨海默病 海马亚区 脑脊液 Β-淀粉样蛋白 TAU蛋白 

分 类 号：R749.16[医药卫生—神经病学与精神病学]