Sex Differences in Alzheimer's Disease: Insights From the Multiomics Landscape.
Sex Differences in Alzheimer's Disease: Insights From the Multiomics Landscape.
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阿尔茨海默病的性别差异：来自多组学领域的见解。
DOI：
10.1016/j.biopsych.2021.02.968
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发表时间：
2022-01-01
影响因子：
10.6
通讯作者：
Cai D
中科院分区：
文献类型：
--
作者：
Guo L;Zhong MB;Zhang L;Zhang B;Cai D
阿尔茨海默病（AD）具有复杂的病因，并且性别对AD的影响在疾病发展过程中有所不同。文献提供了一些证据，性别特异性的贡献，AD。然而，AD性别差异的分子机制仍然难以捉摸。多组学数据与系统生物学方法相结合，为研究AD的性别分层分子机制和开发AD的性别特异性诊断和治疗策略提供了新的途径。单细胞转录组数据集和大量组织转录组数据的细胞去卷积提供了对脑细胞类型特异性对AD中性别偏倚差异的影响的额外见解。在这篇综述中，我们总结了性染色体和性激素对AD的影响，AD发展过程中性别偏见差异的影响，以及性别与主要AD遗传风险因素APOE ε4基因型之间的相互作用，通过多组学景观。一些性别偏见的分子途径，如神经炎症和生物能量代谢已被确定。性染色体和性激素的重要性，以及相关的途径在AD发病机制，进一步加强了从组学研究的结果。未来的研究工作应该使用系统生物学方法整合来自不同脑区和不同细胞类型的多组学数据，并利用这些知识全面检查AD的性别差异。系统生物学技术的进步和日益可用的大规模多组学数据集将促进未来的研究剖析此类复杂的信号机制，以更好地了解两种性别的AD发病机制，最终目标是开发有效的性别和APOE分层预防和治疗干预措施。AD。
Alzheimer’s disease (AD) has complex etiologies, and the impact of sex on AD varies over the course of disease development. The literature provides some evidence of sex-specific contributions to AD. However, molecular mechanisms of sex-biased differences in AD remain elusive. Multiomics data in tandem with systems biology approaches offer a new avenue to dissect sex-stratified molecular mechanisms of AD and to develop sex-specific diagnostic and therapeutic strategies for AD. Single-cell transcriptomic datasets and cell deconvolution of bulk tissue transcriptomic data provide additional insights into brain cell type–specific impact on sex-biased differences in AD. In this review, we summarize the impact of sex chromosomes and sex hormones on AD, the impact of sex-biased differences during AD development, and the interplay between sex and a major AD genetic risk factor, the APOE ε4 genotype, through the multiomics landscape. Several sex-biased molecular pathways such as neuroinflammation and bioenergetic metabolism have been identified. The importance of sex chromosome and sex hormones, as well as the associated pathways in AD pathogenesis, is further strengthened by findings from omics studies. Future research efforts should integrate the multiomics data from different brain regions and different cell types using systems biology approaches, and leverage the knowledge into a holistic examination of sex differences in AD. Advances in systems biology technologies and increasingly available large-scale multiomics datasets will facilitate future studies dissecting such complex signaling mechanisms to better understand AD pathogenesis in both sexes, with the ultimate goals of developing efficacious sex- and APOE-stratified preventive and therapeutic interventions for AD.
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影响因子：
3.7
作者：
Boks MP;Derks EM;Weisenberger DJ;Strengman E;Janson E;Sommer IE;Kahn RS;Ophoff RA
通讯作者：
Ophoff RA
影响因子：
6.8
作者：
Bonham LW;Karch CM;Fan CC;Tan C;Geier EG;Wang Y;Wen N;Broce IJ;Li Y;Barkovich MJ;Ferrari R;Hardy J;Momeni P;Höglinger G;Müller U;Hess CP;Sugrue LP;Dillon WP;Schellenberg GD;Miller BL;Andreassen OA;Dale AM;Barkovich AJ;Yokoyama JS;Desikan RS;International FTD-Genomics Consortium (IFGC);International Parkinson’s Disease Genetics Consortium (IPDGC);International Genomics of Alzheimer’s Project (IGAP)
通讯作者：
International Genomics of Alzheimer’s Project (IGAP)
DOI：
10.1038/nri2394
发表时间：
2008-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Fish EN
通讯作者：
Fish EN
影响因子：
4.3
作者：
Brooks, Lavida R. K.;Mias, George, I
通讯作者：
Mias, George, I
影响因子：
9.8
作者：
Dumanski JP;Lambert JC;Rasi C;Giedraitis V;Davies H;Grenier-Boley B;Lindgren CM;Campion D;Dufouil C;European Alzheimer’s Disease Initiative Investigators;Pasquier F;Amouyel P;Lannfelt L;Ingelsson M;Kilander L;Lind L;Forsberg LA
通讯作者：
Forsberg LA