Lim Key-Hwan, Kim Sung-Hyun, Yang Sumin, Chun Sungkun, Joo Jae-Yeol
Neurodegenerative Disease Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea.
Department of Physiology, Jeonbuk National University Medicine School, Jeonju, 54907, Republic of Korea.
Neurosci Lett. 2021 Apr 1;749:135715. doi: 10.1016/j.neulet.2021.135715. Epub 2021 Feb 15.
Alzheimer's disease (AD) is a common neurodegenerative disease that lacks biomarkers for diagnosis. Biomarkers for accurate detection of AD are required for potential therapeutic approaches. Recent studies in mammalian cells have demonstrated an association between the expression of cell cycle proteins and AD occurrence. Therefore, we aimed to identify a potent biomarker among relevant cell cycle-regulating proteins such as cyclin-dependent kinases (CDKs) for the diagnosis of AD. We also developed a multiplex-PCR-based diagnostic method, which showed the rapid and accurate detection of AD biomarkers. Genome-wide association study (GWAS) results showed increased gene expression of CDKs in an AD mouse model. Based on genomic analysis, our multiplex-PCR method, which contained optimized primer sets and PCR conditions targeting genes of CDKs, accurately matched RT-PCR results in the AD mouse model. Interestingly, validation by in silico meta-analysis for the expression of each CDK gene showed significant expression in moderate and severe groups of AD patients. Accordingly, clinical applications relying on the diagnosis of AD using our results may shed light on AD therapeutics.
阿尔茨海默病（AD）是一种常见的神经退行性疾病，缺乏用于诊断的生物标志物。潜在的治疗方法需要能够准确检测AD的生物标志物。最近在哺乳动物细胞中的研究表明，细胞周期蛋白的表达与AD的发生之间存在关联。因此，我们旨在在相关的细胞周期调节蛋白（如细胞周期蛋白依赖性激酶（CDK））中鉴定一种有效的生物标志物用于AD的诊断。我们还开发了一种基于多重PCR的诊断方法，该方法能够快速准确地检测AD生物标志物。全基因组关联研究（GWAS）结果显示，AD小鼠模型中CDK的基因表达增加。基于基因组分析，我们的多重PCR方法包含针对CDK基因的优化引物组和PCR条件，与AD小鼠模型中的RT-PCR结果准确匹配。有趣的是，通过对每个CDK基因表达的计算机荟萃分析进行验证，结果显示在AD患者的中度和重度组中有显著表达。因此，依靠我们的结果进行AD诊断的临床应用可能会为AD治疗带来启示。
