Transcriptional signatures of brain aging and Alzheimer's disease: What are our rodent models telling us?
Transcriptional signatures of brain aging and Alzheimer's disease: What are our rodent models telling us?
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DOI：
10.1016/j.bbr.2016.05.007
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发表时间：
2017-03-30
影响因子：
2.7
通讯作者：
Blalock EM
中科院分区：
文献类型：
--
作者：
Hargis KE;Blalock EM
衰老是特发性阿尔茨海默病（AD）的最大危险因素。最近，美国国立卫生研究院发布了AD研究建议，包括：欣赏正常的大脑衰老，扩大数据驱动的研究，使用开放获取资源，以及评估实验的可重复性。人类和动物模型中衰老和AD的转录组数据集可在NIH策划的，可访问的数据库中获得。然而，很少有工作已经做了测试这些分子签名之间的一致性。在这里，我们测试的假设，从动物模型的大脑转录概况概括在人类条件下观察到的。分析了来自29项研究的原始转录谱数据，以产生年轻与老年或对照与AD条件的p值和倍数变化。在三个水平上评估了谱间的一致性：1）观察到的显著基因数量与偶然预期的数量; 2）显示方向一致性的显著基因比例; 3）显著基因间效应大小的研究相关性。最高的一致性被发现在受试者的大脑区域。尽管人类、大鼠和小鼠之间的时间老化存在深刻差异，但正常的大脑老化在研究、大脑区域和物种之间是一致的。特发性AD的人类研究在脑结构和研究中是一致的，但与转基因AD小鼠模型的转录谱不一致。此外，评估的五种转基因AD小鼠模型彼此不一致。这些结果表明，人类和研究动物的正常脑老化是相似的，不同的转基因AD模型小鼠可能反映了AD病理学的某些方面。
Aging is the biggest risk factor for idiopathic Alzheimer’s disease (AD). Recently, the National Institutes of Health released AD research recommendations that include: appreciating normal brain aging, expanding data-driven research, using open-access resources, and evaluating experimental reproducibility. Transcriptome data sets for aging and AD in humans and animal models are available in NIH-curated, publically accessible databases. However, little work has been done to test for concordance among those molecular signatures. Here, we test the hypothesis that brain transcriptional profiles from animal models recapitulate those observed in the human condition. Raw transcriptional profile data from twenty-nine studies were analyzed to produce p-values and fold changes for young vs. aged or control vs. AD conditions. Concordance across profiles was assessed at three levels: 1) # of significant genes observed vs. # expected by chance; 2) proportion of significant genes showing directional agreement; 3) correlation among studies for magnitude of effect among significant genes. The highest concordance was found within subjects across brain regions. Normal brain aging was concordant across studies, brain regions, and species, despite profound differences in chronological aging among humans, rats and mice. Human studies of idiopathic AD were concordant across brain structures and studies, but were not concordant with the transcriptional profiles of transgenic AD mouse models. Further, the five transgenic AD mouse models that were assessed were not concordant with one another. These results suggest that normal brain aging is similar in humans and research animals, and that different transgenic AD model mice may reflect selected aspects of AD pathology.
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影响因子：
9.3
作者：
Giunta B;Fernandez F;Nikolic WV;Obregon D;Rrapo E;Town T;Tan J
通讯作者：
Tan J
菌株背景影响表达四环素反式激活蛋白的小鼠的神经毒性和行为异常。
DOI：
10.1523/jneurosci.0893-12.2012
发表时间：
2012-08-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
Han HJ;Allen CC;Buchovecky CM;Yetman MJ;Born HA;Marin MA;Rodgers SP;Song BJ;Lu HC;Justice MJ;Probst FJ;Jankowsky JL
通讯作者：
Jankowsky JL
DOI：
10.1523/jneurosci.3588-11.2011
发表时间：
2011-11-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
Giusti-Rodríguez P;Gao J;Gräff J;Rei D;Soda T;Tsai LH
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Tsai LH
深度测序揭示了单细胞转录组变化的细胞类型特异性模式。
影响因子：
12.3
作者：
Dueck H;Khaladkar M;Kim TK;Spaethling JM;Francis C;Suresh S;Fisher SA;Seale P;Beck SG;Bartfai T;Kuhn B;Eberwine J;Kim J
通讯作者：
Kim J
DOI：
10.1073/pnas.1508249112
发表时间：
2016-01-05
影响因子：
11.1
作者：
Chen, Cho-Yi;Logan, Ryan W.;McClung, Colleen A.
通讯作者：
McClung, Colleen A.