1. Down-regulation of SORL1 is associated with Alzheimer’s disease through activating ABC transporter pathway
- Author
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Boyu Zheng, Xin Li, Bingxin Xie, Shihe Jiang, Xiaohui Liao, Guangming Zhang, Qi Zhang, Xiulian Li, Chen Xu, Xiaoshuang Xia, Xugang Sun, Shijun Zhai, Xingdi Qi, Zhu Ai, Ling Wang, Zhiqiang Wei, and Yan Chen
- Subjects
Genetics ,0303 health sciences ,Candidate gene ,SORL1 ,Down-Regulation ,Membrane Transport Proteins ,ATP-binding cassette transporter ,Methylation ,DNA Methylation ,Biology ,Gene mutation ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Structural variation ,03 medical and health sciences ,0302 clinical medicine ,Alzheimer Disease ,Databases, Genetic ,ABC Transporter Pathway ,Humans ,ATP-Binding Cassette Transporters ,Gene ,LDL-Receptor Related Proteins ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
Alzheimer’s disease (AD) is a common neurodegenerative disease with high morbidity among elderly people. A genetic attribution has been extensively proved. Here, we propose to further prioritize genes that harbor single nucleotide variation (SNV) or structural variation (SV) for AD and explore the underlying potential mechanisms through exploiting their expression and methylation spectra. A high-confidence AD-associated candidate gene list was obtained from the ClinVar and Human Gene Mutation Database (HGMD). Genome-wide methylation and expression profiles of AD and normal subjects were downloaded from the Gene Expression Omnibus (GEO). Through comprehensive comparison of expression and methylation levels between AD and normal samples, as well as different stages of AD samples, SORL1 was identified as the most plausible gene for AD incidence and progression. Gene Set Enrichment Analysis (GSEA) revealed significant activation of the ABC (ATP binding cassette) transporter with the aberrant up-regulation of SORL1 within AD samples. This study unfolds the expression and methylation spectra of previously probed genes with SNV or SV in AD for the first time, and reports an aberrant activation of the ABC transporter pathway that might contribute to AD progression. This should shed some light on AD diagnosis and precision treatment.
- Published
- 2020