JNNP:症状前和症状家族性阿尔茨海默病的血浆GFAP,一项纵向队列研究

2022-09-14 网络 网络

胶质纤维酸性蛋白(GFAP)是星形胶质细胞活化的标志物,已被认为是阿尔茨海默病(AD)的生物标志物。有症状的疾病中,GFAP表达与Aβ斑块密度和脑脊液(CSF)浓度升高相关。测量血浆GFAP

胶质纤维酸性蛋白(GFAP)是星形胶质细胞活化的标志物,已被认为是阿尔茨海默病(AD)的生物标志物。有症状的疾病中,GFAP表达与Aβ斑块密度和脑脊液(CSF)浓度升高相关。测量血浆GFAP的超灵敏测定显示AD的增加相对大于CSF。常染色体显性遗传家族性AD(FAD)是表征症状前AD的一个有价值的模型,因为突变具有高度渗透性,且发病年龄年轻、可合理预测。本文检查了突变携带者与非携带者相比血浆GFAP浓度是否发生变化,以及症状前变化的时间。本文发表在《神经病学,神经外科学和精神病学杂志》上()。

研究了伦敦大学学院2010年至2019年间对FAD的纵向研究中的69名参与者;如前所述。合格性是(1)FAD的临床诊断或(2)受FAD影响的父母,这意味着遗传突变的风险为50%,从而在与受影响父母相似的年龄出现症状。使用Sanger测序确定FAD突变状态;参与者和研究临床医生对结果不知情。在每次研究访视时,进行EDTA血液取样以及参与者和知情者访谈。血浆样品冷冻运送至萨尔格伦斯卡大学医院,在HD-X平台(Quanterix)上使用GFAP单分子阵列发现试剂盒(#102336)进行盲法分析。通过从受试者采血时的年龄中减去受试者受影响父母首次出现渐进性认知症状的年龄,计算出症状出现的估计年数(EYO)。

为每个参与者组(症状突变携带者、症状前携带者和非携带者)制作基线统计数据和GFAP浓度方框图。其他分析使用了所有访问的数据。GFAP被对数变换,估计系数被反变换并表示为乘法效应和几何平均值。在非携带者中,评估了GFAP与性别之间的关系。年龄调整和性别调整(1)患者组之间GFAP的差异以及(2)GFAP和EYO之间的关系均采用混合效应模型进行建模。估计了年龄调整和性别调整后的携带者和非携带者之间的几何平均GFAP的差异,EYO的整数值介于-30和20之间。这一估计值在统计学上显著不同于零(p≤0.05)被谨慎地解释为当载波的GFAP的估计轨迹偏离非载波时的指示。敏感性分析重新调整了所有模型,忽略了具有高异常GFAP值的参与者(一名症状突变携带者,一名非携带者)。

50名参与者无症状(23名突变携带者,27名非携带者对照)。基线和纵向观察到的GFAP数据如图1A、B所示。在非携带者中,女性的估计平均血浆GFAP高于男性(高54%,95%) CI 2%至133%,p=0.039),忽略异常值后无显著差异。在调整就诊年龄和性别后,与非携带者相比,有症状和症状前携带者的几何平均GFAP浓度估计更高(两项比较均p<0.001)。去除两个异常值后,这些结果仍然显著。16岁EYO时,携带者中年龄和性别调整后的几何平均GFAP浓度首次显著高于非携带者(p=0.04)。

(A) 观察到的基线血浆GFAP浓度的方框图(B) 观察到的血浆GFAP浓度与症状发作前后的估计年数。(C) 血浆GFAP的痕迹与发病前/发病后的估计年数

与非携带者相比,症状前和症状性突变携带者的血浆GFAP均升高,与症状前携带者比较,症状性携带者血浆GFAP升高。在估计症状发作前16年左右,携带者和非携带者之间的血浆GFAP水平出现差异。这与最近发现的淀粉样蛋白阳性与淀粉样蛋白阴性认知正常老年人血浆GFAP较高的结果一致,且GFAP增加与随后的整体认知下降、淀粉样蛋白累积和转化为痴呆有关。总的来说,这些结果支持血浆GFAP是早期AD病理学的生物标志物。GFAP变化的时间与淀粉样蛋白的反应一致,支持先前的发现,即血浆GFAP与淀粉样物质负荷和p-tau181水平相关。此外,血浆水平部分介导淀粉样蛋白负荷和tau正电子发射断层扫描(PET)信号之间的关联,并且在淀粉样蛋白阴性、tau阳性个体或路易体痴呆和额颞痴呆中不增加。这表明血浆GFAP是淀粉样相关星形胶质细胞增生的标志物。然而,血浆GFAP也可能是血脑屏障和/或淋巴功能障碍的指标。星形胶质细胞构成神经血管单元的一部分,并可能直接将GFAP释放到血液中,这可能解释了血浆GFAP与脑脊液GFAP的增加幅度更大,以及血浆GFAP和其他脑脊液炎症标志物之间缺乏相关性。

FAD中的血浆GFAP浓度在症状前增加,在估计症状发作前十年检测到变化,支持其作为AD相关星形胶质细胞激活的可获得生物标志物的进一步研究。

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    2023-04-30 mnda
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    2023-02-09 mgqwxj
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    2022-09-16 wetgdt
  8. [GetPortalCommentsPageByObjectIdResponse(id=1818270, encodeId=043618182e075, 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=54, 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 Jan 07 08:18:12 CST 2023, time=2023-01-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1970984, encodeId=36f819e098498, content=<a href='/topic/show?id=4e1ee98203' target=_blank style='color:#2F92EE;'>#GFAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, 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 Apr 30 02:18:12 CST 2023, time=2023-04-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1968686, encodeId=ae5c1968686d2, content=<a href='/topic/show?id=bf70e24322' target=_blank style='color:#2F92EE;'>#FAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7243, encryptionId=bf70e24322, topicName=FAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=669d219, createdName=mgqwxj, createdTime=Thu Feb 09 19:18:12 CST 2023, time=2023-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2077943, encodeId=4d9720e79432c, content=<a href='/topic/show?id=7bff464353a' target=_blank style='color:#2F92EE;'>#家族性阿尔茨海默病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46435, encryptionId=7bff464353a, topicName=家族性阿尔茨海默病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e03212, createdName=liao1619, createdTime=Mon Nov 28 08:18:12 CST 2022, time=2022-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1817247, encodeId=2083181e24706, 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=34, 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=Tue Apr 11 06:18:12 CST 2023, time=2023-04-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470621, encodeId=196414e0621ae, 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=46, 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 Sep 16 14:18:12 CST 2022, time=2022-09-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1629603, encodeId=d9fd1629603a3, content=<a href='/topic/show?id=c61d4641821' target=_blank style='color:#2F92EE;'>#家族性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46418, encryptionId=c61d4641821, topicName=家族性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=26fc21339997, createdName=wetgdt, createdTime=Fri Sep 16 14:18:12 CST 2022, time=2022-09-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1249088, encodeId=dc2b124908868, content=研究很实用, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=40a48324902, createdName=ms9000000200852343, createdTime=Thu Sep 15 14:48:24 CST 2022, time=2022-09-15, status=1, ipAttribution=)]
    2022-09-15 ms9000000200852343

    研究很实用

    0

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