Neuron:重磅发现!阿兹海默病的真正元凶找到了?

2018-06-24 佚名 学术经纬

阿兹海默病是新药研发人员难以逾越的鸿沟。早在 100 多年前,人们就已发现了它的存在。但直到现在,我们依旧没有开发出一款有效预防或治疗这种神经退行性疾病的新药。更夸张的是,最近一系列临床试验的失利表明,β淀粉样蛋白这个过去几十年的主攻方向,可能压根就不是真正的病因。可以说在阿兹海默病面前,人类显得一筹莫展。

阿兹海默病是新药研发人员难以逾越的鸿沟。早在 100 多年前,人们就已发现了它的存在。但直到现在,我们依旧没有开发出一款有效预防或治疗这种神经退行性疾病的新药。更夸张的是,最近一系列临床试验的失利表明,β淀粉样蛋白这个过去几十年的主攻方向,可能压根就不是真正的病因。可以说在阿兹海默病面前,人类显得一筹莫展。

昨天,在线发表在《细胞》出版社旗下《Neuron》期刊上的一项研究,则用大数据的方法,向我们揭示了一个不可思议的潜在致病原因——病毒感染。这篇论文一经刊出,立刻引起了广泛关注与讨论,并得到了《纽约时报》等知名媒体的报道。


▲该研究得到了《纽约时报》等知名媒体的报道(图片来源:《纽约时报》官网截图)

在这项研究里,科学家们首先对 944 个大脑样本进行了分析,其中 622 个样本来自阿兹海默病患者,322 个样本来自健康捐献者。他们做了两个测试,第一个是分析 DNA,了解两者的遗传信息有何不同;第二个是分析 RNA,了解两者的基因表达水平是否一致。值得一提的是,兼具如此数量与深度的大脑样本分析,这还是头一回。

分析结果发现了一个非常有趣的现象:患者与健康人的基因表达模式有明显不同,这并不令人奇怪。但出人意料之外的是,这些改变似乎与病毒感染有关。


▲本研究的负责人 Joel T. Dudley 教授(图片来源:By Claudia Paul (From the photographer) [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons)

“我想要找到(治疗阿兹海默病的)新药,但我找到的只有这些愚蠢的病毒。”本研究的负责人 Joel T. Dudley 教授半开玩笑地说道。他坦言自己只是一名“玩大数据的”,并不是什么阿兹海默病的专家。但就是这名“圈外人”,或许找到了阿兹海默病的关键。

发现阿兹海默病可能与病毒感染有关后,Dudley 教授的团队开始寻找可能参与发病的病毒类型。在患者大脑样本中,他们发现人类疱疹病毒(HHV)6A 与 7 水平明显上升,且与阿兹海默病的症状呈正相关。这些病毒在大脑中做什么呢?科学家们发现,它们在脑细胞里,能影响 BACE1、PSEN1、APBB2 等经典的“阿兹海默病基因”的表达。也就是说,我们看到的许多症状,有可能仅仅是病毒感染带来的后果。


▲诸多“阿兹海默病基因”会被病毒所影响(图片来源:《Neuron》)

这一下子就给人们敲响了警钟。要知道,很少有人能逃过这一大类病毒的感染。它们会在人体内潜伏很长一段时间,并在衰弱时突然爆发。如果它意外地突破血脑屏障,就可能会带来阿兹海默病的风险。

美国国立衰老研究所的负责人 Richard Hodes 博士指出,这是首个用大数据和无偏见(unbiased)的方法,用有力证据表明病原体参与阿兹海默病的研究。另一些学者则说,病毒可能触发了大脑中的免疫反应,激活了这些阿兹海默病基因,导致症状。


▲病毒感染可能在阿兹海默病的发病中扮演了重要角色(图片来源:Graphic by Shireen Dooling for the Biodesign Institute at ASU)

需要注意的是,仅依靠目前的证据,我们尚无法证明病毒感染直接导致了阿兹海默病。但本项研究,以及另一篇即将在下个月出炉的论文,清楚地表明了病毒在其中的重要作用。“这些病毒可能是驱动阿兹海默病患者免疫系统的重要角色。” Dudley 教授补充道。

如果这一机理最终得到证实,那对于阿兹海默病研究领域而言可以说是颠覆性的发现。我们将以全新的角度去看待阿兹海默病的发病,并寻找大脑中潜在的病毒、细菌、以及寄生虫等感染。针对这些感染,我们有望带来治疗阿兹海默病的全新药物,而不必将注意力都花在制造β淀粉样蛋白的基因上。

至少,一些分析已经让我们看到了希望。在今年 4 月发表的一篇论文上,来自中国台湾地区的科学家们发表了一项长期大型研究的结果——在 30000 多人里,感染疱疹病毒的患者,罹患老年失智症的风险是对照组的 2.6 倍。而在使用抗病毒药的群体中,这一风险降低了 90%。

也许,是我们把阿兹海默病想得太复杂了。

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    2019-01-17 by2021
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    2018-06-26 kafei

    学习了谢谢分享

    0

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    2018-06-26 xxxx1054
  5. [GetPortalCommentsPageByObjectIdResponse(id=1735481, encodeId=243d1e35481ff, content=<a href='/topic/show?id=7f019e71750' target=_blank style='color:#2F92EE;'>#阿兹海默病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97717, encryptionId=7f019e71750, topicName=阿兹海默病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9ff833907849, createdName=xre2019, createdTime=Mon Nov 12 05:09:00 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1751865, encodeId=13061e51865ac, content=<a href='/topic/show?id=9b6a12e0155' target=_blank style='color:#2F92EE;'>#Neuron#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12701, encryptionId=9b6a12e0155, topicName=Neuron)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c9c736410065, createdName=by2021, createdTime=Thu Jan 17 00:09:00 CST 2019, time=2019-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=327090, encodeId=7bad32e0905d, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Tue Jun 26 07:28:08 CST 2018, time=2018-06-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549341, encodeId=1ea5154934146, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Tue Jun 26 02:09:00 CST 2018, time=2018-06-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=326853, encodeId=be093268538d, content=谢谢分享.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Mon Jun 25 09:02:33 CST 2018, time=2018-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=326634, encodeId=8d5a32663449, content=学习了.长知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sun Jun 24 12:20:26 CST 2018, time=2018-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=326629, encodeId=0a1332662999, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Sun Jun 24 11:58:29 CST 2018, time=2018-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=326612, encodeId=4b1f326612ec, content=谢谢分享.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Sun Jun 24 11:25:44 CST 2018, time=2018-06-24, status=1, ipAttribution=)]
    2018-06-25 明月清辉

    谢谢分享.学习了

    0

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    2018-06-24 1ddf0692m34(暂无匿称)

    学习了.长知识

    0

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    2018-06-24 医者仁心5538

    学习了

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1735481, encodeId=243d1e35481ff, content=<a href='/topic/show?id=7f019e71750' target=_blank style='color:#2F92EE;'>#阿兹海默病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97717, encryptionId=7f019e71750, topicName=阿兹海默病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9ff833907849, createdName=xre2019, createdTime=Mon Nov 12 05:09:00 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1751865, encodeId=13061e51865ac, content=<a href='/topic/show?id=9b6a12e0155' target=_blank style='color:#2F92EE;'>#Neuron#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12701, encryptionId=9b6a12e0155, topicName=Neuron)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c9c736410065, createdName=by2021, createdTime=Thu Jan 17 00:09:00 CST 2019, time=2019-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=327090, encodeId=7bad32e0905d, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Tue Jun 26 07:28:08 CST 2018, time=2018-06-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549341, encodeId=1ea5154934146, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Tue Jun 26 02:09:00 CST 2018, time=2018-06-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=326853, encodeId=be093268538d, content=谢谢分享.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Mon Jun 25 09:02:33 CST 2018, time=2018-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=326634, encodeId=8d5a32663449, content=学习了.长知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sun Jun 24 12:20:26 CST 2018, time=2018-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=326629, encodeId=0a1332662999, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Sun Jun 24 11:58:29 CST 2018, time=2018-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=326612, encodeId=4b1f326612ec, content=谢谢分享.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Sun Jun 24 11:25:44 CST 2018, time=2018-06-24, status=1, ipAttribution=)]
    2018-06-24 明月清辉

    谢谢分享.学习了

    0

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