Sex differences in the progression of glucose metabolism dysfunction in Alzheimer's disease.
Sex differences in the progression of glucose metabolism dysfunction in Alzheimer's disease.
复制标题
DOI：
10.1038/s12276-023-00993-3
复制
发表时间：
2023-05
影响因子：
12.8
通讯作者：
Mook-Jung, Inhee
中科院分区：
文献类型：
--
作者：
Park, Jong-Chan;Lim, Hanbyeol;Byun, Min Soo;Yi, Dahyun;Byeon, Gihwan;Jung, Gijung;Kim, Yu Kyeong;Lee, Dong Young;Han, Sun-Ho;Mook-Jung, Inhee
阿尔茨海默病（Alzheimer's disease，AD）是一种常见的神经退行性疾病，以淀粉样斑块和脑代谢受损为特征。由于女性AD的患病率高于男性，因此性别差异引起了极大的兴趣。使用横截面和纵向数据，我们显示了AD患者大脑中的性别依赖性代谢失调。队列1（韩国，n = 181）在基线和2年随访时接受匹兹堡化合物B-PET、氟脱氧葡萄糖-PET、磁共振成像和血液生物标志物（血浆tau和β-淀粉样蛋白42和40）测量。对队列2和队列3（欧洲人，n = 78;新加坡人，n = 18）的数据进行转录组分析，发现AD相关脑代谢改变存在性别差异。在女性中（而非男性），所有影像学指标均显示与AD进展一致的相关曲线。在两年的随访中，仅在女性中发现了明显的脑代谢障碍，血浆β-淀粉样蛋白42/40比值可能是女性脑代谢的生物标志物。此外，我们的转录组分析揭示了AD患者大脑中转录组和代谢的性别差异，以及25个女性特异性葡萄糖代谢基因（FGG）的分子网络。我们发现了四个关键吸引子FGG基因（ALDOA，ENO2，PRKACB和PPP2R5D）与淀粉样蛋白/tau相关基因（APP，MAPT，BACE1和BACE2）相关。此外，这些基因成功地区分了女性中的淀粉样蛋白阳性。了解AD发病机制中的性别差异并考虑这些差异将有助于开发有效的AD诊断和治疗方法。在阿尔茨海默病患者中发现的代谢和基因活性改变的性别差异可能有助于揭示为什么这种疾病在女性中比男性更普遍。由首尔国立大学的Inhee Mook-Jung和Sun-Ho Han领导的韩国研究人员在对181名韩国人进行为期两年的脑部扫描和血液测试后发现，只有女性的葡萄糖代谢明显受损。另一项对78名欧洲患者和18名新加坡患者的基因活性进行的研究发现了25个参与葡萄糖代谢的女性特异性基因。其中四个基因在导致阿尔茨海默病患者脑细胞中发现的淀粉样蛋白和tau蛋白异常积累的事件中发挥作用。这些结果可以提高阿尔茨海默病的诊断，并有助于指导不同患者群体选择最合适的干预措施。
Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by amyloid plaques and impaired brain metabolism. Because women have a higher prevalence of AD than men, sex differences are of great interest. Using cross-sectional and longitudinal data, we showed sex-dependent metabolic dysregulations in the brains of AD patients. Cohort 1 (South Korean, n = 181) underwent Pittsburgh compound B-PET, fluorodeoxyglucose-PET, magnetic resonance imaging, and blood biomarker (plasma tau and beta-amyloid 42 and 40) measurements at baseline and two-year follow-ups. Transcriptome analysis of data from Cohorts 2 and 3 (European, n = 78; Singaporean, n = 18) revealed sex differences in AD-related alterations in brain metabolism. In women (but not in men), all imaging indicators displayed consistent correlation curves with AD progression. At the two-year follow-up, clear brain metabolic impairment was revealed only in women, and the plasma beta-amyloid 42/40 ratio was a possible biomarker for brain metabolism in women. Furthermore, our transcriptome analysis revealed sex differences in transcriptomes and metabolism in the brains of AD patients as well as a molecular network of 25 female-specific glucose metabolic genes (FGGs). We discovered four key-attractor FGG genes (ALDOA, ENO2, PRKACB, and PPP2R5D) that were associated with amyloid/tau-related genes (APP, MAPT, BACE1, and BACE2). Furthermore, these genes successfully distinguished amyloid positivity in women. Understanding sex differences in the pathogenesis of AD and considering these differences will improve development of effective diagnostics and therapeutic treatments for AD. Sex-dependent differences in altered metabolism and gene activity found in patients with Alzheimer’s disease might help reveal why the disease is more prevalent in females than males. Researchers in South Korea led by Inhee Mook-Jung and Sun-Ho Han at Seoul National University found clearly impaired glucose metabolism only in females during a two-year monitoring of 181 South Koreans involving brain scans and blood tests. A separate study of gene activity in 78 European and 18 Singaporean patients identified 25 female-specific genes involved in glucose metabolism. Four of these genes have a role in the events leading to abnormal accumulations of amyloid and tau proteins found in brain cells in Alzheimer’s patients. The results could enhance diagnosis of Alzheimer’s disease and help guide the choice of the most appropriate interventions for different patient groups.
登录
查看更多内容
影响因子：
7.4
作者：
Li, Rena;Singh, Meharvan
通讯作者：
Singh, Meharvan
影响因子：
9.9
作者：
Barnes, LL;Wilson, RS;Bennett, DA
通讯作者：
Bennett, DA
影响因子：
9.9
作者：
Doecke, James D.;Perez-Grijalba, Virginia;Sarasa, Manuel
通讯作者：
Sarasa, Manuel
影响因子：
--
作者：
Gao, S;Hendrie, HC;Hall, KS
通讯作者：
Hall, KS
影响因子：
4.8
作者：
De Felice FG;Lourenco MV
通讯作者：
Lourenco MV