Peripheral level of CD33 and Alzheimer's disease: a bidirectional two-sample Mendelian randomization study.
Peripheral level of CD33 and Alzheimer's disease: a bidirectional two-sample Mendelian randomization study.
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CD33和阿尔茨海默氏病的外围水平：一项双向孟德尔随机研究。
DOI：
10.1038/s41398-022-02205-4
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发表时间：
2022-10-03
影响因子：
6.8
通讯作者：
Chen, Yongping
中科院分区：
文献类型：
--
作者：
Gu, Xiaojing;Dou, Meng;Cao, Bei;Jiang, Zheng;Chen, Yongping
脑中CD 33表达的增加被认为与淀粉样斑块负荷的增加有关，而阿尔茨海默病（AD）患者外周CD 33水平及其在AD中的作用尚不清楚。本研究旨在系统探讨外周血CD 33与AD的双向关系。AD的全基因组关联研究（GWAS）数据集（N例：21982; N对照：41944）、血液CD 33 mRNA水平、血浆CD 33蛋白水平和免疫细胞亚型上的CD 33表达来自在欧洲人群中进行的GWAS。从GWAS中提取合格的IV。MR估计值通过逆方差加权（IVW）和其他敏感性分析计算。使用TwoSampleMR进行主要统计分析（v.0.5.5）在R包中（V.4.1.2）.在前向MR分析中，（CD 33作为暴露量，AD作为结果），IVW结果表明血CD 33 mRNA水平升高（OR [95% CI] = 1.156[1.080，1.238]，p = 3.25e-05），血清CD 33蛋白水平升高（OR [95%CI] = 1.08 [1.031，1.139]，p = 1.6e-03）和免疫细胞亚型上CD 33表达增加（p < 0.05）均导致AD的风险增加。敏感性分析支持这些发现。而反向MR分析（AD为暴露，CD 33为转归）表明AD并不导致血液中CD 33蛋白水平的升高（p > 0.05）。总之，我们的研究结果表明，外周表达的CD 33的升高是导致AD的发展。未来的研究需要将CD 33作为AD的生物标志物和治疗靶点。
Increased expression of CD33 in the brain has been suggested to be associated with increased amyloid plaque burden, while the peripheral level of CD33 in Alzheimer’s disease (AD) patients and its role in AD remain unclear. The current study aimed to systematically explore the bidirectional relationship between peripheral CD33 and AD. Genome-wide association study (GWAS) datasets of AD (Ncases: 21982; Ncontrols: 41944), blood CD33 mRNA level, the plasma CD33 protein level, and CD33 expression on immune-cell subtypes were obtained from GWASs conducted in the European population. Eligible IVs were extracted from the GWASs. MR estimates were calculated by inverse-variance weighting (IVW) and other sensitivity analyses. The main statistical analyses were conducted using TwoSampleMR (v.0.5.5) in R package (V.4.1.2).In the forward MR analysis (CD33 as exposure and AD as outcome), the IVW results indicated that elevated blood CD33 mRNA level (OR [95% CI] = 1.156[1.080, 1.238], p = 3.25e-05), elevated serum CD33 protein level (OR [95% CI] = 1.08 [1.031, 1.139], p = 1.6e-03) and increased CD33's expression on immune cell subtypes (p < 0.05) were all leading to a higher risk of AD. And sensitivity analyses supported these findings. While the reverse MR analysis (AD as exposure and CD33 as outcome) indicated that AD was not leading to the elevation of CD33's protein level in the blood (p > 0.05). In conclusion, our results indicated that elevated peripheral expression of CD33 was causal to the development of AD. Future studies are needed to work on developing CD33 as a biomarker and therapeutic target in AD.
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免疫细胞中自身免疫和疗法的复杂遗传特征。
影响因子：
30.8
作者：
Orrù V;Steri M;Sidore C;Marongiu M;Serra V;Olla S;Sole G;Lai S;Dei M;Mulas A;Virdis F;Piras MG;Lobina M;Marongiu M;Pitzalis M;Deidda F;Loizedda A;Onano S;Zoledziewska M;Sawcer S;Devoto M;Gorospe M;Abecasis GR;Floris M;Pala M;Schlessinger D;Fiorillo E;Cucca F
通讯作者：
Cucca F
影响因子：
10.6
作者：
Karch CM;Goate AM
通讯作者：
Goate AM
DOI：
10.1038/s41572-021-00269-y
发表时间：
2021-05-13
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Knopman DS;Amieva H;Petersen RC;Chételat G;Holtzman DM;Hyman BT;Nixon RA;Jones DT
通讯作者：
Jones DT
影响因子：
30.8
作者：
Verbanck M;Chen CY;Neale B;Do R
通讯作者：
Do R
影响因子：
--
作者：
Burgess, Stephen;Davey Smith, George;Theodoratou, Evropi
通讯作者：
Theodoratou, Evropi