Alzheimer's & Dementia:华山医院团队揭示阿尔茨海默氏症的血脂生物标记物

2020-09-21 haibei MedSci原创

目前仍缺乏方便的途径或生物标志物来识别认知功能下降,尤其是在阿尔茨海默病(AD)谱系的早期阶段。

认知能力下降是一个逐渐积累的病理过程,包括无声无息地发展为轻度认知功能障碍(MCI)和痴呆症。以数据为导向的调查显示,在美国和中国的65岁以上人群中,轻度认知功能障碍和痴呆症的患病率分别为20%-30%和8%。此外,全球老龄化人口的快速增长也加速了认知功能障碍的患病率。然而,目前仍缺乏方便的途径或生物标志物来识别认知功能下降,尤其是在阿尔茨海默病(AD)谱系的早期阶段。

值得注意的是,血液中的代谢物被认为是症状前病理过程的生物标志物,有助于识别早期或晚期认知轨迹较差的个体,从而提高临床试验和早期干预的效率。

参与脂质运输和代谢的载脂蛋白编码基因的多态性,如载脂蛋白E(APOE)和簇蛋白(CLU),被认为与AD的风险增加有关,表明脂质代谢在早期诊断中的潜在预测作用。

随着质谱技术和分析软件的进步,一些新型平台已经使用非靶向或靶向脂质组学方法分析疾病过程和相关生物标志物。多平台筛选调查已经确定了磷脂酰胆碱(PC)分子在诊断MCI和AD中的作用,支持PC代谢异常与正常衰老中记忆表现和认知功能差的特定关联。同样,一项脂质组学研究表明,将AD患者与对照组区分开来的血浆代谢物分子主要来自脂质,如胆固醇酯(CE),AD患者的血浆鞘脂(SP16)水平相对下降,而神经酰胺(CM16)水平上升。

脑脊液(CSF)生物标志物采样的侵入性程序,和昂贵的成像检查,如淀粉样蛋白成像的正电子发射断层扫描(PET),迄今为止一般没有被应用于筛查或确定认知能力下降的高危人群。

最近,来自华山医院的研究团队在Alzheimer's & Dementia杂志发文,旨在通过追踪认知老化的轨迹,确定一个全面的脂质信号模式,而不是单个分子,作为认知衰退的预测因子。

研究人员分析了来自阿尔茨海默病神经影像学倡议(ADNI)数据库的374名非痴呆参与者的579个血浆脂质数据。为了额外验证这些血浆脂质在预测认知能力差方面的有效性,研究人员还检查了所选脂质与AD表型的关联。

研究人员使用最小绝对收缩和选择算子逻辑回归模型来选择最能表征认知衰退(由认知的快速年率定义)的脂质。通过使用该模型,研究人员构建了脂质总结评分作为认知衰退的预测因子。多变量调整模型测试了风险评分与AD表型的关联。

最终,该研究中纳入了17种选定脂质的模型显示出良好的辨别和校准能力。血脂风险评分与基线阿尔茨海默病评估量表-13项认知子量表(ADAS-Cog13)评分和脑脊液tau蛋白水平呈正相关,并能预测认知诊断。

其他结果也显示,血脂风险评分增加的个体,ADAS-Cog13和脑萎缩的变化率较快,进一步证实了血脂的预测作用。

因此,该队列研究表明。通过多个血脂特征,而不是单个脂质分子,可以更好地诊断和预测认知能力下降。

 

 

原始出处:

Ya‐Hui Ma et al. A panel of blood lipids associated with cognitive performance, brain atrophy, and Alzheimer's diagnosis: A longitudinal study of elders without dementia. Alzheimer's & Dementia (2020). DOI: https://doi.org/10.1002/dad2.12041

 

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attachment=null, authenticateStatus=null, createdAvatar=, createdBy=278f2500221, createdName=12498fa0m11暂无昵称, createdTime=Wed Sep 23 11:22:25 CST 2020, time=2020-09-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1349958, encodeId=6bb01349958a6, content=<a href='/topic/show?id=3a59693e129' target=_blank style='color:#2F92EE;'>#生物标记物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69371, encryptionId=3a59693e129, topicName=生物标记物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=55ce62, createdName=hbwxf, createdTime=Wed Sep 23 11:22:25 CST 2020, time=2020-09-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470411, encodeId=3be814e0411f6, 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=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Wed Sep 23 11:22:25 CST 2020, time=2020-09-23, status=1, ipAttribution=)]
    2021-06-14 wjywjy
  4. 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encodeId=01e788e28523, content=所以是不是相当于用了多个血脂相关蛋白进行了模型构建?<a href='/topic/show?id=54068020409' target=_blank style='color:#2F92EE;'>#老年痴呆症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=290, replyNumber=2, topicName=null, topicId=null, topicList=[TopicDto(id=80204, encryptionId=54068020409, topicName=老年痴呆症)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210607/9f00a0de660e4b36b77a9a5f7620d6bf/98c22b17ddf7446fa7b9a618fabcb9f7.jpg, createdBy=a8fb2299762, createdName=Psycho.Dr Du, createdTime=Tue Sep 22 09:05:32 CST 2020, time=2020-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1345421, encodeId=d9f713454213e, content=<a href='/topic/show?id=8907693e0fa' target=_blank style='color:#2F92EE;'>#生物标记#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69370, encryptionId=8907693e0fa, topicName=生物标记)], 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replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Wed Sep 23 11:22:25 CST 2020, time=2020-09-23, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1817034, encodeId=5b90181e034c3, 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=33, 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 Aug 17 14:22:25 CST 2021, time=2021-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1717970, encodeId=17f41e179702e, content=<a href='/topic/show?id=8f0658433a' target=_blank style='color:#2F92EE;'>#dementia#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, 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encodeId=01e788e28523, content=所以是不是相当于用了多个血脂相关蛋白进行了模型构建?<a href='/topic/show?id=54068020409' target=_blank style='color:#2F92EE;'>#老年痴呆症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=290, replyNumber=2, topicName=null, topicId=null, topicList=[TopicDto(id=80204, encryptionId=54068020409, topicName=老年痴呆症)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210607/9f00a0de660e4b36b77a9a5f7620d6bf/98c22b17ddf7446fa7b9a618fabcb9f7.jpg, createdBy=a8fb2299762, createdName=Psycho.Dr Du, createdTime=Tue Sep 22 09:05:32 CST 2020, time=2020-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1345421, encodeId=d9f713454213e, content=<a href='/topic/show?id=8907693e0fa' target=_blank style='color:#2F92EE;'>#生物标记#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69370, encryptionId=8907693e0fa, topicName=生物标记)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=278f2500221, createdName=12498fa0m11暂无昵称, createdTime=Wed Sep 23 11:22:25 CST 2020, time=2020-09-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1349958, encodeId=6bb01349958a6, content=<a href='/topic/show?id=3a59693e129' target=_blank style='color:#2F92EE;'>#生物标记物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69371, encryptionId=3a59693e129, topicName=生物标记物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=55ce62, createdName=hbwxf, createdTime=Wed Sep 23 11:22:25 CST 2020, time=2020-09-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470411, encodeId=3be814e0411f6, 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=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Wed Sep 23 11:22:25 CST 2020, time=2020-09-23, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1817034, encodeId=5b90181e034c3, 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=33, 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 Aug 17 14:22:25 CST 2021, time=2021-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1717970, encodeId=17f41e179702e, content=<a href='/topic/show?id=8f0658433a' target=_blank style='color:#2F92EE;'>#dementia#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, 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encodeId=01e788e28523, content=所以是不是相当于用了多个血脂相关蛋白进行了模型构建?<a href='/topic/show?id=54068020409' target=_blank style='color:#2F92EE;'>#老年痴呆症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=290, replyNumber=2, topicName=null, topicId=null, topicList=[TopicDto(id=80204, encryptionId=54068020409, topicName=老年痴呆症)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210607/9f00a0de660e4b36b77a9a5f7620d6bf/98c22b17ddf7446fa7b9a618fabcb9f7.jpg, createdBy=a8fb2299762, createdName=Psycho.Dr Du, createdTime=Tue Sep 22 09:05:32 CST 2020, time=2020-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1345421, encodeId=d9f713454213e, content=<a href='/topic/show?id=8907693e0fa' target=_blank style='color:#2F92EE;'>#生物标记#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69370, encryptionId=8907693e0fa, topicName=生物标记)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=278f2500221, createdName=12498fa0m11暂无昵称, createdTime=Wed Sep 23 11:22:25 CST 2020, time=2020-09-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1349958, encodeId=6bb01349958a6, content=<a href='/topic/show?id=3a59693e129' target=_blank style='color:#2F92EE;'>#生物标记物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69371, encryptionId=3a59693e129, topicName=生物标记物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=55ce62, createdName=hbwxf, createdTime=Wed Sep 23 11:22:25 CST 2020, time=2020-09-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470411, encodeId=3be814e0411f6, 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=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Wed Sep 23 11:22:25 CST 2020, time=2020-09-23, status=1, ipAttribution=)]
    2020-09-22 Psycho.Dr Du

    所以是不是相当于用了多个血脂相关蛋白进行了模型构建?#老年痴呆症#

    2

    展开2条回复
  7. 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  8. 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  9. 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