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.

中文翻译：

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SORL1 下调通过激活 ABC 转运蛋白通路与阿尔茨海默病相关

阿尔茨海默病（AD）是一种常见的神经退行性疾病，在老年人中发病率很高。遗传归因已被广泛证明。在这里，我们建议进一步优先考虑具有单核苷酸变异 (SNV) 或结构变异 (SV) 的 AD 基因，并通过利用它们的表达和甲基化谱来探索潜在的潜在机制。从 ClinVar 和人类基因突变数据库 (HGMD) 中获得了高度可信的 AD 相关候选基因列表。AD 和正常受试者的全基因组甲基化和表达谱从基因表达综合 (GEO) 下载。通过综合比较AD样本与正常样本，以及AD样本不同阶段的表达和甲基化水平，SORL1 被确定为 AD 发病率和进展最合理的基因。基因集富集分析 (GSEA) 显示 ABC（ATP 结合盒）转运蛋白显着激活，AD 样品中 SORL1 异常上调。这项研究首次揭示了之前在 AD 中探测到的 SNV 或 SV 基因的表达和甲基化谱，并报告了可能导致 AD 进展的 ABC 转运蛋白通路的异常激活。这应该对 AD 诊断和精准治疗有所启发。这项研究首次揭示了之前在 AD 中探测到的 SNV 或 SV 基因的表达和甲基化谱，并报告了可能导致 AD 进展的 ABC 转运蛋白通路的异常激活。这应该对 AD 诊断和精准治疗有所启发。这项研究首次揭示了之前在 AD 中探测到的 SNV 或 SV 基因的表达和甲基化谱，并报告了可能导致 AD 进展的 ABC 转运蛋白通路的异常激活。这应该对 AD 诊断和精准治疗有所启发。