A molecular network of the aging human brain provides insights into the pathology and cognitive decline of Alzheimer's disease.
A molecular network of the aging human brain provides insights into the pathology and cognitive decline of Alzheimer's disease.
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DOI：
10.1038/s41593-018-0154-9
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发表时间：
2018-06
影响因子：
25
通讯作者：
De Jager PL
中科院分区：
文献类型：
--
作者：
Mostafavi S;Gaiteri C;Sullivan SE;White CC;Tasaki S;Xu J;Taga M;Klein HU;Patrick E;Komashko V;McCabe C;Smith R;Bradshaw EM;Root DE;Regev A;Yu L;Chibnik LB;Schneider JA;Young-Pearse TL;Bennett DA;De Jager PL
需要新的治疗靶点来预防阿尔茨海默病（AD），这是导致与衰老相关的认知能力下降的主要原因。在这里，我们报告了衰老人类额叶皮层分子网络的构建和验证。利用来自 478 名个体的 RNA 序列数据，我们首先使用共表达基因模块构建了一个分子网络，然后将这些模块与 AD 及其神经病理学和认知内表型联系起来。我们在两个独立的 AD 数据集以及表观基因组数据中确认了这些关联。我们还说明了该网络在优先考虑淀粉样蛋白相关基因以在人类神经元和星形胶质细胞中进行体外验证中的用途。这些基于独特队列的分析使我们能够区分对 AD 病理积累有直接影响的不同皮质模块与对认知能力下降有直接影响的不同皮质模块的作用，举例说明了复杂疾病的网络方法。对衰老人类皮质的 RNA 测序数据进行系统生物学分析，确定了一个分子网络，该网络优先考虑影响阿尔茨海默病认知衰退或神经病理学的基因组。
There is a need for new therapeutic targets with which to prevent Alzheimer’s disease (AD), a major contributor to aging-related cognitive decline. Here, we report the construction and validation of a molecular network of the aging human frontal cortex. Using RNA sequence data from 478 individuals, we first build a molecular network using modules of coexpressed genes and then relate these modules to AD and its neuropathologic and cognitive endophenotypes. We confirm these associations in two independent AD datasets as well as in epigenomic data. We also illustrate the use of the network in prioritizing amyloid-associated genes for in vitro validation in human neurons and astrocytes. These analyses based on unique cohorts enable us to resolve the role of distinct cortical modules that have a direct effect on the accumulation of AD pathology from those that have a direct effect on cognitive decline, exemplifying a network approach to complex diseases. Systems biology analysis of RNA sequencing data from the aging human cortex identifies a molecular network which prioritizes groups of genes that influence cognitive decline or neuropathology in Alzheimer’s disease.
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影响因子：
11.2
作者：
Chibnik, Lori B.;Shulman, Joshua M.;Leurgans, Sue E.;Schneider, Julie A.;Wilson, Robert S.;Tran, Dong;Aubin, Cristin;Buchman, Aron S.;Heward, Christopher B.;Myers, Amanda J.;Hardy, John A.;Huentelman, Matthew J.;Corneveaux, Jason J.;Reiman, Eric M.;Evans, Denis A.;Bennett, David A.;De Jager, Philip L.
通讯作者：
De Jager, Philip L.
影响因子：
7
作者：
Battle A;Mostafavi S;Zhu X;Potash JB;Weissman MM;McCormick C;Haudenschild CD;Beckman KB;Shi J;Mei R;Urban AE;Montgomery SB;Levinson DF;Koller D
通讯作者：
Koller D
影响因子：
11.2
作者：
Bennett, David A.;Wilson, Robert S.;Boyle, Patricia A.;Buchman, Aron S.;Schneider, Julie A.
通讯作者：
Schneider, Julie A.
影响因子：
12.3
作者：
Gustafsson M;Nestor CE;Zhang H;Barabási AL;Baranzini S;Brunak S;Chung KF;Federoff HJ;Gavin AC;Meehan RR;Picotti P;Pujana MÀ;Rajewsky N;Smith KG;Sterk PJ;Villoslada P;Benson M
通讯作者：
Benson M
影响因子：
4.6
作者：
Gaiteri C;Chen M;Szymanski B;Kuzmin K;Xie J;Lee C;Blanche T;Chaibub Neto E;Huang SC;Grabowski T;Madhyastha T;Komashko V
通讯作者：
Komashko V