血浆和脑脊液中自身抗tau抗体的自然发生规律及对阿尔茨海默病的启示  

Regularity of naturally occurring auto-antibodies against tau in plasma and cerebrospinal fluid and its implication in Alzheimer's disease

作　　者：陈伟明 周丽华 徐武华 CHEN Weiming;ZHOU Lihua;XU Wuhua(Department of Rehabilitation Medicine(Neurology Ⅱ),Guangzhou RedCross Hospital,Guangzhou 510220,China;Department of Neurology Guangdong 999 Brain Hospital,Guangzhou 510510,China)

机构地区：[1]广州市红十字会医院康复医学科(神内二区),广东广州510220 [2]广东三九脑科医院神经内科,广东广州510510

出　　处：《分子影像学杂志》2022年第6期944-949,共6页Journal of Molecular Imaging

基　　金：广东省自然科学基金(S201210008985);广州市科技计划项目(201604020100)。

摘　　要：目的探讨自身抗tau抗体(nAb-tau)的免疫特性、自然发生规律以及对阿尔茨海默病(AD)的临床诊断价值。方法选取我院2006~2018年临床资料完整并符合美国国立神经病学与语言障碍、卒中和阿尔茨海默病及相关疾病协会及相关标准,同时获取血浆和脑脊液(CSF)标本的5例AD患者、5例其他痴呆(OD)患者和10例正常认知受试者(NC组),进行Westernblot检测;选取20例NC组按10岁为年龄段根据分层随机法分为7组作为对照组,进行血浆免疫组化染色(IHC)。以全序列的tau441为标准抗原,上述研究对象的血浆(1∶1000)和CSF(1∶5000)作为一抗,Westernblot定性检测nAb-tau带,均同时设置单克隆抗tau抗体(AT-8)和PBS为阳性对照和阴性对照。结果Westernblot检测结果显示,3组CSF中仅其他痴呆组1例未检出nAb-tau阳性带,3组CSF中nAb-tau(+)检出率之间的差异无统计学意义(χ^(2)=3.158,P=0.206),CSF中nAb-tau(+)检出率均明显高于血浆(P<0.001),血浆nAb-tau(+)带均出现在NC组(χ^(2)=2.222,P=0.329);血浆和CSF的nAb-tau检出率与简易智力状态检查(MMSE)均分之间的相关性无统计学意义;IHC结果显示,NC组均完成血浆的IHC分析,阳性率为55%(11/20),但以10岁为一个年龄段将NC组划分为7个年龄段组,7组的血浆IHC阳性率差异无统计学意义(χ^(2)=4.512,P=0.608)。结论在自然衰老过程中nAb-tau无差别出现在各个年龄段,且CSF的检出率显著高于血浆,但因缺乏疾病组间差异以及与MMSE分值之间关联,不足以作为阿尔茨海默病生物学诊断标志物。Objective To evaluate the immunological characteristics,natural occurrence and clinical diagnostic value of naturally occurring auto-antibodies against tau(nAb-tau)in Alzheimer's disease(AD).Methods Western blot was performed to detect the expression of antibodies in plasma and cerebrospinal fluid of 5 AD patients,5 other dementia(OD)patients and 10 normal cognitive subjects(NC).These subjects came from our hospital with complete clinical data from 2006 to 2018 and met the National Institute of Neurology and Language Disorders,Stroke,Alzheimer's Disease and Related Diseases and related standards.20 NC patients were divided into 7 groups according to the stratified random method according to the age range of-10 as the control group to complete immunohistochemistry(IHC)of plasma.The whole sequence of tau441 was used as the standard antigen,and the plasma(1∶1000)and CSF(1∶5000)of the above subjects were used as the primary antibodies.The nAb-tau bands were qualitatively detected by Western blot.Both monoclonal anti-tau antibody(AT-8)and PBS were set as positive and negative controls at the same time.Result(1)Western blot results:Only 1 case of OD group wasn't detected nAb tau positive band in CSF,showing no statistically significant differences in the detection rate of nAb-tau(+)in the CSF of 3 groups(χ²=3.158,P=0.206).The detection rate of nAb-tau(+)in CSF was significantly higher than that in plasma(P<0.001),but all plasma nAb-tau(+)bands appeared in NC group(χ^(2)=2.222,P=0.329);The differences between the detection rate ofnAb-tau and the mean score of the MMSE lacks statistical significance.(2)IHC results:The NC group completed the plasma IHC analysis,with a positive rate of 55%(11/20).However,the NC group was divided into 7 age groups with the age of 10 years.There was no statistically significant difference between the plasma IHC positive rates of the 7 groups(χ^(2)=4.512,P=0.608).Conclusion In the process of natural aging,nAb-tau has no difference in all age groups,and the detection rate of CSF is sig

关 键 词：阿尔茨海默病 自身抗tau抗体 免疫印迹 免疫组化染色 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R446.6[医药卫生—临床医学]