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Sci Adv:华人学者带来阿兹海默病创新诊断工具

2017-08-30 佚名 药明康德

阿兹海默病是全球影响范围最广的老年失智症,在全球有超过4000万名患者。由于其病因至今尚不完全确定,因此也没有有效的治疗手段。同时由于该病影响患者的认知、行为、日常功能和生理学等多个方面,确诊阿兹海默病也不是一件容易的事情。

阿兹海默病是全球影响范围最广的老年失智症,在全球有超过4000万名患者。由于其病因至今尚不完全确定,因此也没有有效的治疗手段。同时由于该病影响患者的认知、行为、日常功能和生理学等多个方面,确诊阿兹海默病也不是一件容易的事情。

目前对于阿兹海默病的诊断主要依靠医生对于患者出现的症状的观察,加上一些认知功能和情感功能的测试,这一过程中并没有可以依赖的定量指标。此外,由于不是所有的患者都会出现这些症状,并且还需要与正常衰老过程区分,对于阿兹海默病的诊断并不精确,很大程度上依赖于医生的经验和判断。


▲本研究的主要负责人张明君教授(图片来源:OSU)

最近,来自美国俄亥俄州立大学的华人学者张明君教授团队发表了一项新研究,它通过计算机算法,整合了这个团队新发现的生物标记物,并辅以患者的认知功能测试,能对阿兹海默病进行诊断,并能预测患者的病情发展。这个新方法发表在了《科学》杂志子刊《Science Advances》上。

在这项研究中,张明君教授的团队采集了24名阿兹海默病患者和10名健康志愿者的脑脊液和血液样本,并收集了他们的医疗记录,包括多年来的神经学检查和认知功能测试结果。


▲本研究的设计流程(图片来源:《Science Advances》)

研究人员首先使用了多种纳米级别的检测技术在患者的血液和脑脊液样本中寻找那些与阿兹海默病有关的生物标记物。他们从患者的脑脊液样本中分离了蛋白聚合物,分析发现阿兹海默病患者与健康志愿者相比,脑脊液中蛋白聚合物的数量更多,尺寸更大。接下来他们使用原子力显微镜测量了这些蛋白聚合物的刚度,结果发现,阿兹海默病患者脑脊液中的蛋白聚合物刚度更高,并且刚度和病情严重程度呈明显的正相关。这些发现符合患者脑部的病理学发展,即阿兹海默病的进程伴随着β淀粉样蛋白和tau蛋白的聚积和纤维化。

在患者的血液样本中,研究人员使用了包裹着β淀粉样蛋白的原子力显微镜探针来检测血液中的β淀粉样蛋白含量。结果发现阿兹海默病患者血液中的β淀粉样蛋白含量少于健康志愿者。这也符合关于阿兹海默病的传统观点,即随着病情发展,更多的β淀粉样蛋白会聚积在患者脑部,导致血液中β淀粉样蛋白含量下降。


▲研究人员表示,与医生诊断相比,该工具的稳定度更高(图片来源:《Science Advances》)

随后,研究人员开发了一个基于卡尔曼滤波的算法,他们将每位患者的生物标记物和认知功能测试历史输入了计算机,并以此对患者的病情严重程度做出诊断。他们发现,患者接受认知测试的次数越多,诊断的正确率越高。在拥有超过6次就诊记录的患者中,这一算法的诊断错误率已经降到了5%以下,研究人员认为,继续增加测试次数能够提高的诊断正确率非常有限。通过分析这些患者的病情发展过程,这个算法还能够预测
每位患者的接下来的病情发展,并提出最佳的复诊时间。这些数据将在保证医生能够掌握患者病情发展的前提下,最大限度的提高医院和医生的效率。


▲张明君教授与他的团队有望带来更多突破(图片来源:OSU)

张明君教授表示:“先前,我们还不能预测疾病的发展有多快,但这个工具可以做到这一点。我们知道每个患者的发展速度是不同的。同时分析与疾病相关的多个指标能够一下子提高诊断和预后分析的可靠性。”

研究人员希望,通过这个算法能够帮助医生尽早诊断阿兹海默病患者并开始治疗。此外,这个算法对于中后期患者病情发展速度的预测,也有望帮助加速针对这一阶段患者的药物研发。

我们希望这项研究能够早日转化为临床应用,帮助阿兹海默病患者和医生更好地了解病情,及时带来有效的疾病控制手段。
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Sep 01 01:28:00 CST 2017, time=2017-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1581972, encodeId=889615819e294, content=<a href='/topic/show?id=830c35868ec' target=_blank style='color:#2F92EE;'>#华人#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=35868, encryptionId=830c35868ec, topicName=华人)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3f7716881423, createdName=ms4468361851264128, createdTime=Fri Sep 01 01:28:00 CST 2017, time=2017-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1623005, encodeId=b9da162300551, content=<a href='/topic/show?id=54a7358e4cb' target=_blank style='color:#2F92EE;'>#华人学者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=35874, encryptionId=54a7358e4cb, topicName=华人学者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4c1720449156, createdName=zhangxingru, createdTime=Fri Sep 01 01:28:00 CST 2017, time=2017-09-01, status=1, ipAttribution=)]
    2017-10-24 rgjl
  4. 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createdBy=c37033510464, createdName=surilei, createdTime=Thu Aug 09 01:28:00 CST 2018, time=2018-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1915272, encodeId=399219152e28c, content=<a href='/topic/show?id=e381586e94d' target=_blank style='color:#2F92EE;'>#新诊断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58679, encryptionId=e381586e94d, topicName=新诊断)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8b48400, createdName=rgjl, createdTime=Tue Oct 24 02:28:00 CST 2017, time=2017-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=240710, encodeId=66a5240e109e, content=好文.值得点赞!认真学习了.把经验应用于实践.为患者解除病痛., beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30251637888, createdName=lietome15, createdTime=Tue Sep 05 11:52:26 CST 2017, time=2017-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=240506, encodeId=6ffd24050626, content=基础的东西说的很好.但是到临床不知道有多少路.还有可能是歪路., beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/31/208d170d6afc2977ff569bbd0fe70ce1.jpg, createdBy=6e811377745, createdName=qinxyang, createdTime=Mon Sep 04 22:44:22 CST 2017, time=2017-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=239348, encodeId=ef7d239348f9, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0a61971598, createdName=往日如昨, createdTime=Fri Sep 01 14:59:59 CST 2017, time=2017-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=239244, encodeId=995a23924466, content=认真学习.不断进步.把经验分享给同好.点赞了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30251637888, createdName=lietome15, createdTime=Fri Sep 01 08:08:54 CST 2017, time=2017-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1285405, encodeId=d61a128540584, content=<a href='/topic/show?id=77903209422' target=_blank style='color:#2F92EE;'>#创新#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32094, encryptionId=77903209422, topicName=创新)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=512a199, createdName=lilianxiang, createdTime=Fri Sep 01 01:28:00 CST 2017, time=2017-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1581972, encodeId=889615819e294, content=<a href='/topic/show?id=830c35868ec' target=_blank style='color:#2F92EE;'>#华人#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=35868, encryptionId=830c35868ec, topicName=华人)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3f7716881423, createdName=ms4468361851264128, createdTime=Fri Sep 01 01:28:00 CST 2017, time=2017-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1623005, encodeId=b9da162300551, content=<a href='/topic/show?id=54a7358e4cb' target=_blank style='color:#2F92EE;'>#华人学者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=35874, encryptionId=54a7358e4cb, topicName=华人学者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4c1720449156, createdName=zhangxingru, createdTime=Fri Sep 01 01:28:00 CST 2017, time=2017-09-01, status=1, ipAttribution=)]
    2017-09-05 lietome15

    好文.值得点赞!认真学习了.把经验应用于实践.为患者解除病痛.

    0

  5. 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createdBy=30251637888, createdName=lietome15, createdTime=Tue Sep 05 11:52:26 CST 2017, time=2017-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=240506, encodeId=6ffd24050626, content=基础的东西说的很好.但是到临床不知道有多少路.还有可能是歪路., beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/31/208d170d6afc2977ff569bbd0fe70ce1.jpg, createdBy=6e811377745, createdName=qinxyang, createdTime=Mon Sep 04 22:44:22 CST 2017, time=2017-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=239348, encodeId=ef7d239348f9, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0a61971598, createdName=往日如昨, createdTime=Fri Sep 01 14:59:59 CST 2017, time=2017-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=239244, encodeId=995a23924466, content=认真学习.不断进步.把经验分享给同好.点赞了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30251637888, createdName=lietome15, createdTime=Fri Sep 01 08:08:54 CST 2017, time=2017-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1285405, encodeId=d61a128540584, content=<a href='/topic/show?id=77903209422' target=_blank style='color:#2F92EE;'>#创新#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32094, encryptionId=77903209422, topicName=创新)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=512a199, createdName=lilianxiang, createdTime=Fri Sep 01 01:28:00 CST 2017, time=2017-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1581972, encodeId=889615819e294, content=<a href='/topic/show?id=830c35868ec' target=_blank style='color:#2F92EE;'>#华人#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=35868, encryptionId=830c35868ec, topicName=华人)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3f7716881423, createdName=ms4468361851264128, createdTime=Fri Sep 01 01:28:00 CST 2017, time=2017-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1623005, encodeId=b9da162300551, content=<a href='/topic/show?id=54a7358e4cb' target=_blank style='color:#2F92EE;'>#华人学者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=35874, encryptionId=54a7358e4cb, topicName=华人学者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4c1720449156, createdName=zhangxingru, createdTime=Fri Sep 01 01:28:00 CST 2017, time=2017-09-01, status=1, ipAttribution=)]
    2017-09-04 qinxyang

    基础的东西说的很好.但是到临床不知道有多少路.还有可能是歪路.

    0

  6. 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createdBy=c37033510464, createdName=surilei, createdTime=Thu Aug 09 01:28:00 CST 2018, time=2018-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1915272, encodeId=399219152e28c, content=<a href='/topic/show?id=e381586e94d' target=_blank style='color:#2F92EE;'>#新诊断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58679, encryptionId=e381586e94d, topicName=新诊断)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8b48400, createdName=rgjl, createdTime=Tue Oct 24 02:28:00 CST 2017, time=2017-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=240710, encodeId=66a5240e109e, content=好文.值得点赞!认真学习了.把经验应用于实践.为患者解除病痛., beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30251637888, createdName=lietome15, createdTime=Tue Sep 05 11:52:26 CST 2017, time=2017-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=240506, encodeId=6ffd24050626, content=基础的东西说的很好.但是到临床不知道有多少路.还有可能是歪路., beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/31/208d170d6afc2977ff569bbd0fe70ce1.jpg, createdBy=6e811377745, createdName=qinxyang, createdTime=Mon Sep 04 22:44:22 CST 2017, time=2017-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=239348, encodeId=ef7d239348f9, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0a61971598, createdName=往日如昨, createdTime=Fri Sep 01 14:59:59 CST 2017, time=2017-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=239244, encodeId=995a23924466, content=认真学习.不断进步.把经验分享给同好.点赞了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30251637888, createdName=lietome15, createdTime=Fri Sep 01 08:08:54 CST 2017, time=2017-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1285405, encodeId=d61a128540584, content=<a href='/topic/show?id=77903209422' target=_blank style='color:#2F92EE;'>#创新#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32094, encryptionId=77903209422, topicName=创新)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=512a199, createdName=lilianxiang, createdTime=Fri Sep 01 01:28:00 CST 2017, time=2017-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1581972, encodeId=889615819e294, content=<a href='/topic/show?id=830c35868ec' target=_blank style='color:#2F92EE;'>#华人#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=35868, encryptionId=830c35868ec, topicName=华人)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3f7716881423, createdName=ms4468361851264128, createdTime=Fri Sep 01 01:28:00 CST 2017, time=2017-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1623005, encodeId=b9da162300551, content=<a href='/topic/show?id=54a7358e4cb' target=_blank style='color:#2F92EE;'>#华人学者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=35874, encryptionId=54a7358e4cb, topicName=华人学者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4c1720449156, createdName=zhangxingru, createdTime=Fri Sep 01 01:28:00 CST 2017, time=2017-09-01, status=1, ipAttribution=)]
    2017-09-01 往日如昨

    学习了谢谢分享

    0

  7. 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topicName=华人学者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4c1720449156, createdName=zhangxingru, createdTime=Fri Sep 01 01:28:00 CST 2017, time=2017-09-01, status=1, ipAttribution=)]
    2017-09-01 lietome15

    认真学习.不断进步.把经验分享给同好.点赞了!

    0

  8. 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  9. 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阿兹海默病和帕金森病是两种最为常见的神经退行性疾病,不过,两者的病理特征、影响的大脑部位和临床症状有很大的区别。在阿兹海默病患者脑内,由β淀粉样蛋白形成的斑块和tau蛋白形成的神经缠结导致了位于海马体和前额叶皮层的神经细胞死亡,使患者的认知和记忆功能衰退。而在帕金森病患者中,由α-synuclein蛋白形成的路易氏体主要影响中脑的黑质部分,导致患者的运动功能受损。

Biological Psychiatry:早期检测阿尔兹海默病研究进展

2017年3月27日,国际精神病学《Biological Psychiatry》杂志在线发表了中国科学技术大学申勇教授实验室联合法国巴黎皮埃尔居里大学的 Harald Hampel教授,瑞典哥德堡大学临床神经科学中心的Kaj Blennow,美国佛罗里达州罗斯坎特老年医学研究所李人教授以及美国Emory大学阿尔兹海默病研究中心的Allan Levey 教授等共同发表了题为(Increased

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