SARS-CoV-2 infection increases the gene expression profile for Alzheimer's disease risk.
SARS-CoV-2 infection increases the gene expression profile for Alzheimer's disease risk.
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DOI：
10.1016/j.omtm.2022.09.007
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发表时间：
2022-12-08
期刊：
影响因子：
--
通讯作者：
Mohapatra, Subhra
中科院分区：
文献类型：
--
作者：
Green, Ryan;Mayilsamy, Karthick;McGill, Andrew R.;Martinez, Taylor E.;Chandran, Bala;Blair, Laura J.;Bickford, Paula C.;Mohapatra, Shyam S.;Mohapatra, Subhra
2019冠状病毒病（COVID-19）大流行迄今已在全球造成6亿多例感染。多达30%的轻度至重度疾病患者会发展为长期COVID，表现出包括痴呆症在内的多种神经系统症状。然而，关于脑分子标记物以及这些标记物是否会诱发阿尔茨海默病（AD）的发病，目前还缺乏相关知识。在此，我们报告了COVID-19重症患者的大脑基因表达谱，显示先天免疫反应基因和与AD发病有关的基因表达增加。在老年小鼠模型中使用小鼠适应的SARS-CoV-2 （MA10）菌株显示出病毒嗜神经性，病毒感染时间延长，tau聚集物FKBP51，干扰素诱导基因ifif204以及补体基因C4和C5AR1的表达增加。脑组织病理学显示老年MA10感染小鼠的AD特征包括tau磷酸化、tau寡聚化和α-突触核蛋白表达增加。SARS-CoV-2感染和AD大脑基因表达谱的结果以及MA10老年小鼠模型的研究结果首次提供了证据，表明SARS-CoV-2感染改变了与AD发展相关的大脑基因的表达。未来对SARS-CoV-2感染和阿尔茨海默病共同分子标志物的研究可能有助于开发针对阿尔茨海默病的新疗法。重症COVID-19患者的大脑基因表达谱显示，与阿尔茨海默病发病机制相关的几个基因表达增加。在新型老年小鼠模型中使用小鼠适应的SARS CoV-2 （MA10）毒株，揭示了病毒嗜神经性和阿尔茨海默病病理的证据，包括tau磷酸化和寡聚化。
The coronavirus disease 2019 (COVID-19) pandemic has caused over 600,000,000 infections globally thus far. Up to 30% of individuals with mild to severe disease develop long COVID, exhibiting diverse neurologic symptoms including dementias. However, there is a paucity of knowledge of molecular brain markers and whether these can precipitate the onset of Alzheimer’s disease (AD). Herein, we report the brain gene expression profiles of severe COVID-19 patients showing increased expression of innate immune response genes and genes implicated in AD pathogenesis. The use of a mouse-adapted strain of SARS-CoV-2 (MA10) in an aged mouse model shows evidence of viral neurotropism, prolonged viral infection, increased expression of tau aggregator FKBP51, interferon-inducible gene Ifi204, and complement genes C4 and C5AR1. Brain histopathology shows AD signatures including increased tau-phosphorylation, tau-oligomerization, and α-synuclein expression in aged MA10 infected mice. The results of gene expression profiling of SARS-CoV-2-infected and AD brains and studies in the MA10 aged mouse model taken together, for the first time provide evidence suggesting that SARS-CoV-2 infection alters expression of genes in the brain associated with the development of AD. Future studies of common molecular markers in SARS-CoV-2 infection and AD could be useful for developing novel therapies targeting AD. The brain gene expression profile of severe COVID-19 patients shows increased expression of several genes implicated in Alzheimer’s disease pathogenesis. The use of a mouse-adapted strain of SARS CoV-2 (MA10) in a novel aged mouse model reveals evidence of viral neurotropism and Alzheimer’s pathology including tau phosphorylation and oligomerization.
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影响因子：
15.1
作者：
Hernandez MX;Jiang S;Cole TA;Chu SH;Fonseca MI;Fang MJ;Hohsfield LA;Torres MD;Green KN;Wetsel RA;Mortazavi A;Tenner AJ
通讯作者：
Tenner AJ
影响因子：
64.8
作者：
Hur JY;Frost GR;Wu X;Crump C;Pan SJ;Wong E;Barros M;Li T;Nie P;Zhai Y;Wang JC;Tcw J;Guo L;McKenzie A;Ming C;Zhou X;Wang M;Sagi Y;Renton AE;Esposito BT;Kim Y;Sadleir KR;Trinh I;Rissman RA;Vassar R;Zhang B;Johnson DS;Masliah E;Greengard P;Goate A;Li YM
通讯作者：
Li YM
影响因子：
3.1
作者：
Hur, Ji-Yeun
通讯作者：
Hur, Ji-Yeun
影响因子：
5.3
作者：
Cheng Z;Zou X;Jin Y;Gao S;Lv J;Li B;Cui R
通讯作者：
Cui R
影响因子：
8.4
作者：
Amzat, Jimoh;Aminu, Kafayat;Danjibo, Maryann C.
通讯作者：
Danjibo, Maryann C.