机构：[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China,[2]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China,[3]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China,[4]Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing, China
Alzheimer disease (AD) is the most common cause of dementia and creates a significant burden on society. As a result, the investigation of hub genes for the discovery of potential therapeutic targets and candidate biomarkers is warranted. In this study, we used the ComBat method to merge three gene expression datasets of AD from the Gene Expression Omnibus (GEO). During combined analysis, we identified 850 differentially expressed genes (DEGs) from the temporal cortex of AD and cognitively normal (CN) samples. We performed weighted gene coexpression network analysis to build gene coexpression networks incorporating these DEGs to identify key modules and hub genes. We found one module most strongly correlated with AD onset as the key module and 19 hub genes in the key module that were down-regulated in AD brains. According to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, DEGs were mostly enriched in synapse function, and genes in the key module were mostly related to learning and memory. We selected five little-studied genes,AP3B2,GABRD,GPR158,KIAA0513, andMAL2, to validate their expression in AD mouse model by performing quantitative real-time polymerase chain reaction. We found that all of them were down-regulated in cortices of 8-month 5xFAD mice compared to those of wild-type mice. We then further investigated their correlations with beta-secretase activity and A beta 42 levels in AD samples of different Braak stages. We found that all five hub genes had significant negative associations with beta-secretase activity and thatAP3B2andKIAA0513had significant negative associations with A beta 42 levels. We tested the differential expressions of the five hub genes in two AD GEO datasets from the blood and found thatKIAA0513was significantly up-regulated in patients with both mild cognitive impairment (MCI) and AD and was able to differentiate MCI and AD from CN in the two datasets. In conclusion, these five novel vulnerable genes were involved in AD progression, and KIAA0513 was a promising candidate biomarker for early diagnosis of AD.
基金：
This study was supported by the Key Project of the
National Natural Science Foundation of China (81530036);
the National Key Scientific Instrument and Equipment
Development Project (31627803); the Mission Program of Beijing Municipal Administration of Hospitals (SML20150801);
the Beijing Scholars Program; the Beijing Brain Initiative
from Beijing Municipal Science & Technology Commission
(Z161100000216137); the Project for Outstanding Doctor with
Combined Ability of Western and Chinese Medicine; and the
Beijing Municipal Commission of Health and Family Planning
(PXM2019_026283_000003).
第一作者机构：[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China,
通讯作者：
推荐引用方式(GB/T 7714)：
Min Zhu,Longfei Jia,Fangyu Li,et al.Identification ofKIAA0513and Other Hub Genes Associated With Alzheimer Disease Using Weighted Gene Coexpression Network Analysis[J].FRONTIERS IN GENETICS.2020,11:doi:10.3389/fgene.2020.00981.
APA：
Min Zhu,Longfei Jia,Fangyu Li&Jianping Jia.(2020).Identification ofKIAA0513and Other Hub Genes Associated With Alzheimer Disease Using Weighted Gene Coexpression Network Analysis.FRONTIERS IN GENETICS,11,
MLA：
Min Zhu,et al."Identification ofKIAA0513and Other Hub Genes Associated With Alzheimer Disease Using Weighted Gene Coexpression Network Analysis".FRONTIERS IN GENETICS 11.(2020)
