JNNP:血清GFAP鉴别阿尔茨海默病和额颞叶痴呆并预测MCI到痴呆的转化

2022-05-26 网络 网络

反应性星形胶质细胞增生等神经炎症过程是包括阿尔茨海默病(AD)和额颞叶痴呆(FTD)在内的神经退行性痴呆的常见特征。在AD和FTD的死后脑组织和动物模型中发现了反应性星形胶质细胞,但它们在病理生理学中

反应性星形胶质细胞增生等神经炎症过程是包括阿尔茨海默病(AD)和额颞叶痴呆(FTD)在内的神经退行性痴呆的常见特征。在AD和FTD的死后脑组织和动物模型中发现了反应性星形胶质细胞,但它们在病理生理学中的作用尚不完全清楚。尽管对AD和FTD中现有的星形胶质细胞增生已有多年的认识,但尚不清楚星形胶质细胞增生是否在不同疾病之间有所不同,是否可能是不同病理生理学和临床表型的一个来源。

胶质纤维酸性蛋白(GFAP)是一种中间丝蛋白,主要表达于中枢神经系统的星形胶质细胞中。GFAP在反应性星形胶质细胞中的表达增加,在AD和FTD脑中的表达增加。脑脊液(CSF)等体液中GFAP的测量为研究人类患者一生中的反应性星形胶质细胞增生提供了可能性。最近,血液中GFAP的测量变得更容易获得。脑脊液和血液中GFAP水平的研究已经成功地应用于揭示相关神经退行性疾病中不同的神经炎症特征,也是诊断或预后的候选生物标志物。比较了血液中GFAP水平作为AD和行为变异型FTD(bvFTD)持续性星形胶质细胞增生的标志。

AD患者的GFAP水平增加了一倍,而bvFTD患者的GFAP水平没有增加。在AD患者中,血液中GFAP水平也与认知障碍的程度相关。这表明AD和bvFTD之间反应性星形胶质细胞增生的差异具有病理生理学意义,也可能具有诊断相关性,因为迄今为止的鉴别诊断主要基于临床症状和脑脊液生物标记物。此外,GFAP血液水平与认知障碍的相关性可能有助于疾病分期。尽管在我们的试点研究中观察到了明显的差异,但独立验证大型多中心研究的结果对于评估GFAP对AD和bvFTD的诊断相关性以及与认知障碍的关联性至关重要。此外, 没有研究AD早期的GFAP水平,这将进一步提高我们对早期反应性星形胶质细胞增生的理解。GFAP水平与其他血液标记物的比较有助于阐明反应性星形胶质细胞增生与其他疾病相关机制的关系。这里的两个候选者是神经丝轻链(NfL)和pTau181,它们属于AD和FTD7中研究最深入的血液标记物,与神经变性和淀粉样蛋白/τ病理学两个重要机制有关。

本研究的目的是评估和比较600例以上AD和bvFTD患者的血液GFAP水平变化。此外,还比较了不同AD阶段(轻度认知障碍(MCI)与显性痴呆)的变化,并对认知评分进行相关分析,以评估与疾病进展的关系。通过受试者操作特征(ROC)曲线分析评估血液GFAP作为区分AD和bvFTD的生物标志物的性能,并与NfL和pTau181的血液水平进行比较。本文发表在《神经病学,神经外科学和精神病学杂志》上(

生物标记物支持的AD痴呆诊断和AD所致MCI(MCI-AD)。我们使用临床痴呆评分(CDR)框总和(CDR-SB)或全局CDR将AD患者分为MCI-AD患者(CDR-SB<2.5或CDR全局<1.0)和AD痴呆患者(CDR-SB≥2.5或CDR global≥1.0)。一组MCI-AD患者(n=32)在样本采集(基线)后进行了3.9±2.6年(平均值±标准差)的临床随访。bvFTD队列(n=140)包括47名已知FTD突变的患者(34%),包括16×c9 FTD、11×GRN-FTD、5×MAPT-FTD和15名其他突变的患者。根据制造商的说明,使用Quanterix Simoa HD-1分析仪在Ulm中使用Simoa GFAP发现试剂盒和Simoa pTau-181 V2 Advantage试剂盒测量血清中的GFAP和pTau181。疾病组在不同的分析板上随机分组,所有试验均包括血清QC样品。在测量期间,GFAP的批内和批间CV分别为1.9%–13.1%。

阿尔茨海默病(AD)早期血清胶质纤维酸性蛋白(GFAP)水平升高

本研究共调查了四个临床中心610名患者的样本。与对照组(167 pg/mL,IQR 108-234 pg/mL)和bvFTD(190 pg/mL,IQR 134-298 pg/mL,p<0.001)相比,AD痴呆患者的血清GFAP水平升高(中位数375 pg/mL,IQR 276-505 pg/mL)。GFAP在疾病早期阶段已经增加(MCI-AD,300 pg/mL,IQR 232–433 pg/mL,p<0.001),在随访期间发生痴呆的MCI-AD患者中GFAP更高(360 pg/mL,IQR 253–414 pg/mL vs 215 pg/mL,IQR 111–266 pg/mL,p<0.01,曲线下面积(AUC)=0.77)。血清GFAP对AD的诊断性能(AUC=0.84,敏感性98%,特异性60%,似然比2.5)与血清pTau181相当(AUC=0.89,敏感性80%,特异性87%,似然比6.0),但优于血清NfL(AUC=0.71,敏感性92%,特异性49%,似然比1.8)。和16.6%,pTau181的批内和批间CV分别为4.3%–12.9%和11.6%,分析显示出良好的性能。使用人类NF-L试剂盒,在Ulm中使用ProteinSimple Ella仪器测量血清中的NfL。最近,ELA仪器在不同的神经退行性疾病中得到了验证,产生了与更常用的Simoa NfL分析相当的结果。在测量过程中,将13个疾病组随机分组,所有运行中均包括血清QC样本。该分析显示出良好的性能,批内和批间CV分别为5.2%–10.4%和11.4%。

数据表明AD和bvFTD中存在不同类型的反应性星形胶质细胞增生,并支持血清GFAP作为鉴别诊断和预测MCI向痴呆转化的生物标志物

Oeckl PAnderl-Straub SVon Arnim CAF, et al Serum GFAP differentiates Alzheimer’s disease from frontotemporal dementia and predicts MCI-to-dementia conversion

 

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    2022-09-11 mnda
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  4. [GetPortalCommentsPageByObjectIdResponse(id=1817189, encodeId=8597181e18922, content=<a href='/topic/show?id=17b59e77626' target=_blank style='color:#2F92EE;'>#阿尔茨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97776, encryptionId=17b59e77626, topicName=阿尔茨)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Bnia2EtH2IvyBtniaWHPQOYAicsN3IAL1ZuPV7qyALcdCiawRJdEiafMxWTxzERQW7eeKg8HfCKCRK2CJicy073C4RJg/132, createdBy=464b2500186, createdName=ms1948154235210413, createdTime=Wed Nov 09 01:56:24 CST 2022, time=2022-11-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1970983, encodeId=773919e098311, content=<a href='/topic/show?id=4e1ee98203' target=_blank style='color:#2F92EE;'>#GFAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7982, encryptionId=4e1ee98203, topicName=GFAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6a8d381, createdName=mnda, createdTime=Sun Sep 11 20:56:24 CST 2022, time=2022-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1818212, encodeId=b63d181821205, content=<a href='/topic/show?id=4c9f9e777ac' target=_blank style='color:#2F92EE;'>#阿尔茨海#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97777, encryptionId=4c9f9e777ac, topicName=阿尔茨海)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Sat Nov 12 09:56:24 CST 2022, time=2022-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1968684, encodeId=57da196868466, content=<a href='/topic/show?id=bf70e24322' target=_blank style='color:#2F92EE;'>#FAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7243, encryptionId=bf70e24322, topicName=FAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=669d219, createdName=mgqwxj, createdTime=Wed Apr 26 14:56:24 CST 2023, time=2023-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470560, encodeId=b23614e0560da, content=<a href='/topic/show?id=45a79e7788c' target=_blank style='color:#2F92EE;'>#阿尔茨海默#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5917090900, createdName=yhj-time, createdTime=Fri May 27 13:56:24 CST 2022, time=2022-05-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1519393, encodeId=bc7c1519393f5, content=<a href='/topic/show?id=3731113e8c3' target=_blank style='color:#2F92EE;'>#MCI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11378, encryptionId=3731113e8c3, topicName=MCI)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=934111256894, createdName=hukaixun, createdTime=Fri May 27 13:56:24 CST 2022, time=2022-05-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1222589, encodeId=a4f41222589e8, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Thu May 26 13:19:51 CST 2022, time=2022-05-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1247106, encodeId=8884124e10647, content=老年性痴呆,未来还是希望借助神经电生理吧,也许更为有效!, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=neuro.Dr, createdTime=Thu May 26 01:56:24 CST 2022, time=2022-05-26, status=1, ipAttribution=)]
    2023-04-26 mgqwxj
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    2022-05-27 hukaixun
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    2022-05-26 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

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    2022-05-26 neuro.Dr

    老年性痴呆,未来还是希望借助神经电生理吧,也许更为有效!

    0

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