Alzheimers Dementia:遗传性痴呆,蓝斑核完整性降低,随后tau聚集增加

2022-03-21 网络 网络

LC完整性作为临床前ADAD疾病进展的标志。

阿尔茨海默病(AD)是最常见的痴呆形式,在神经病理学上被定义为淀粉样β(Aβ)斑块和神经纤维缠结的堆积。 在40岁时,几乎每个尸检病例都会在脑室(LC)出现高磷酸化的tau。

然后,在50岁左右,tau出现在脑内皮层,随后在60岁左右,Aβ和tau开始在新皮层累积。 散发性AD的临床症状通常在65岁后开始观察。这些病理和临床症状之间的时间滞后可能是确定何时应开始干预的关键。早期检测和干预对于防止病理的猖獗蔓延和延迟疾病进展至关重要。

在老年人中,包括临床前的散发性AD,用专门的磁共振成像(MRI)方法证明,LC的完整性在54岁时达到高峰并开始下降,这是人生中皮质tau开始出现的时间。 与尸检数据一致,较低的LC完整性与较大的皮质tau结合有关,在尚未检测到Aβ的个体中也是如此。较低的LC强度也预示着记忆力的下降,在出现容易检测的纤维状Aβ-PET(正电子发射断层扫描)水平之前。

携带presenilin-1(PSEN1)突变的个体在成年早期就注定要发展为常染色体显性阿尔茨海默病(ADAD)。虽然散发性AD和ADAD的病理相似,但它们在时间顺序上有所不同。

在ADAD中,Aβ沉积比皮质tau病理早≈10至15年。 已知ADAD的皮质tau病变发生在发病前9年,在地形上与散发性AD相似,但进展加快。尸检研究尚未系统地检查ADAD的LC,但Theofilas等人(2017)中一个年轻的Braak VI期病例(#63)的LC包括了一个LC。 此外,去甲肾上腺素传输和代谢的改变在散发性和早期发病的AD中很明显,并与tau和认知能力下降有关。

鉴于LC是AD中纠缠前物质的初始部位,而tau与认知密切相关。

藉此, 哈佛大学的 Heidi I.L. Jacobs等人,假设在ADAD中,与年龄相关的LC完整性变化发生在成年早期,在纠缠病理积累之前,但可能在预期的Aβ发病后不久。此外,预计更差的LC完整性将与更大的皮质tau沉积和更差的认知表现相关。

他们在居住在哥伦比亚安提奥基亚的最大的已知血统的PSEN1 E280A(Glu280Ala)突变携带者和年龄匹配的非携带者家庭成员中,使用MRI将LC完整性与Aβ和Tau的PET和认知测量联系起来。

这些携带者的一个子集也有平均2年后的后续成像和认知数据,使的能够评估LC完整性是否与tau的变化相一致,并确定LC完整性是否可能在寻找早期预后标志物方面有希望。

他们发现了:携带者的LC完整性在32岁开始下降,比临床发病早12年,比散发性AD早20年。

LC的完整性与皮质tau呈负相关,与淀粉样β无关,并预测楔前tau的增加。

另外,LC的完整性与记忆力呈正相关。

这些发现支持LC完整性作为临床前ADAD疾病进展的标志。



原文出处:
Jacobs HIL, Becker JA, Kwong K, et al. Waning locus coeruleus integrity precedes cortical tau accrual in preclinical autosomal dominant Alzheimer’s disease. Alzheimer’s & Dementia. Published online March 17, 2022:alz.12656. doi:10.1002/alz.12656

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  4. 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  5. 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content=<a href='/topic/show?id=c157696175' target=_blank style='color:#2F92EE;'>#ERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6961, encryptionId=c157696175, topicName=ERS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e93e105, createdName=anminleiryan, createdTime=Fri May 13 22:23:21 CST 2022, time=2022-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1205535, encodeId=2b0a120553562, content=脑室(LC)应该是蓝斑, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07085560551, createdName=高神经, createdTime=Thu Mar 24 12:01:03 CST 2022, time=2022-03-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1338554, encodeId=8d051338554ba, content=<a 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  6. 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content=<a href='/topic/show?id=c157696175' target=_blank style='color:#2F92EE;'>#ERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6961, encryptionId=c157696175, topicName=ERS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e93e105, createdName=anminleiryan, createdTime=Fri May 13 22:23:21 CST 2022, time=2022-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1205535, encodeId=2b0a120553562, content=脑室(LC)应该是蓝斑, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07085560551, createdName=高神经, createdTime=Thu Mar 24 12:01:03 CST 2022, time=2022-03-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1338554, encodeId=8d051338554ba, content=<a href='/topic/show?id=767711566a9' target=_blank style='color:#2F92EE;'>#MERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11566, encryptionId=767711566a9, topicName=MERS)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/71tKRib0PibveVjnEa7tPLMaCzoKicFlKSEOzRTGf4wNvDV54kJyNx1ott1D5Xp5gRu7IwUia77oN0YFdffvQMu6Ug/132, createdBy=9e302500146, createdName=ms49895894946433513521, createdTime=Wed Mar 23 20:23:21 CST 2022, time=2022-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1509360, encodeId=1e0415093603d, content=<a href='/topic/show?id=19791e14471' target=_blank style='color:#2F92EE;'>#Tau#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17144, encryptionId=19791e14471, topicName=Tau)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Wed Mar 23 20:23:21 CST 2022, time=2022-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1246690, encodeId=aa1e124669075, 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=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=neuro.Dr, createdTime=Tue Mar 22 08:23:21 CST 2022, time=2022-03-22, status=1, ipAttribution=)]
    2022-05-13 anminleiryan
  7. 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authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Wed Mar 23 20:23:21 CST 2022, time=2022-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1246690, encodeId=aa1e124669075, 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=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=neuro.Dr, createdTime=Tue Mar 22 08:23:21 CST 2022, time=2022-03-22, status=1, ipAttribution=)]
    2022-03-24 高神经

    脑室(LC)应该是蓝斑

    0

  8. 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content=<a href='/topic/show?id=c157696175' target=_blank style='color:#2F92EE;'>#ERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6961, encryptionId=c157696175, topicName=ERS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e93e105, createdName=anminleiryan, createdTime=Fri May 13 22:23:21 CST 2022, time=2022-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1205535, encodeId=2b0a120553562, content=脑室(LC)应该是蓝斑, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07085560551, createdName=高神经, createdTime=Thu Mar 24 12:01:03 CST 2022, time=2022-03-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1338554, encodeId=8d051338554ba, content=<a 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    2022-03-23 hb2008ye
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content=<a href='/topic/show?id=c157696175' target=_blank style='color:#2F92EE;'>#ERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6961, encryptionId=c157696175, topicName=ERS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e93e105, createdName=anminleiryan, createdTime=Fri May 13 22:23:21 CST 2022, time=2022-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1205535, encodeId=2b0a120553562, content=脑室(LC)应该是蓝斑, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=07085560551, createdName=高神经, createdTime=Thu Mar 24 12:01:03 CST 2022, time=2022-03-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1338554, encodeId=8d051338554ba, content=<a href='/topic/show?id=767711566a9' target=_blank style='color:#2F92EE;'>#MERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11566, encryptionId=767711566a9, topicName=MERS)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/71tKRib0PibveVjnEa7tPLMaCzoKicFlKSEOzRTGf4wNvDV54kJyNx1ott1D5Xp5gRu7IwUia77oN0YFdffvQMu6Ug/132, createdBy=9e302500146, createdName=ms49895894946433513521, createdTime=Wed Mar 23 20:23:21 CST 2022, time=2022-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1509360, encodeId=1e0415093603d, content=<a href='/topic/show?id=19791e14471' target=_blank style='color:#2F92EE;'>#Tau#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17144, encryptionId=19791e14471, topicName=Tau)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Wed Mar 23 20:23:21 CST 2022, time=2022-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1246690, encodeId=aa1e124669075, 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=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=neuro.Dr, createdTime=Tue Mar 22 08:23:21 CST 2022, time=2022-03-22, status=1, ipAttribution=)]
    2022-03-22 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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