Mori Hiroaki, Yoshino Yuta, Ueno Mariko, Funahashi Yu, Kumon Hiroshi, Ozaki Yuki, Yamazaki Kiyohiro, Ochi Shinichiro, Iga Jun-Ichi, Ueno Shu-Ichi
Department of Neuropsychiatry, Molecules and Function Ehime University Graduate School of Medicine, Shitsukawa Toon Ehime Japan.
PCN Rep. 2022 Dec 14;1(4):e65. doi: 10.1002/pcn5.65. eCollection 2022 Dec.
This study aimed to investigate the expression levels and methylation status of () in the blood of Alzheimer's disease (AD) patients and age- and sex-matched healthy controls.
Fifty AD outpatients and 50 healthy contorls were enrolled. Blood samples were collected for processing of complementary DNA and genomic DNA. messenger ribonucleic acid (mRNA) expression was analyzed by real-time quantitative polymerase chain reaction. The methylation rates of four cytosine-phosphate-guanine (CpG) sites in the upstream region of exon1 were evaluated by the pyrosequencing method.
No significant differences in mRNA expression levels were found between AD and control subjects (AD 0.97 ± 0.49 vs. control 1.0 ± 0.64, = 0.62). mRNA expression levels were not correlated with any other clinical characteristics or results of psychological tests. mRNA expression levels were significantly higher in AD subjects treated with acetylcholinesterase inhibitors (AchEIs) ( = 25) than in subjects not treated with AChEIs ( = 25) (unmedicated 0.83 ± 0.33 vs. medicated 1.12 ± 0.59, = 0.049). The AD subjects did not differ from the control subjects in methylation rates at selected CpG sites. methylation status were not correlated with clinical characteristics, the results of psychological tests, or mRNA expression.
mRNA expression levels and methylation status in blood do not appear useful as biomarkers for AD or the examined CpG sites were not genetically significant for gene expression or AD pathology. However, AChEIs may alter mRNA expression. Further studies are needed to explore blood biomarkers that can discriminate AD patients from controls.
本研究旨在调查阿尔茨海默病(AD)患者及年龄和性别匹配的健康对照者血液中()的表达水平和甲基化状态。
招募了50名AD门诊患者和50名健康对照者。采集血样用于互补DNA和基因组DNA的处理。通过实时定量聚合酶链反应分析信使核糖核酸(mRNA)表达。采用焦磷酸测序法评估外显子1上游区域四个胞嘧啶-磷酸-鸟嘌呤(CpG)位点的甲基化率。
AD患者与对照者之间的mRNA表达水平无显著差异(AD为0.97±0.49,对照为1.0±0.64,=0.62)。mRNA表达水平与任何其他临床特征或心理测试结果均无相关性。接受乙酰胆碱酯酶抑制剂(AchEIs)治疗的AD患者(=25)的mRNA表达水平显著高于未接受AchEIs治疗的患者(=25)(未用药组为0.83±0.33,用药组为1.12±0.59,=0.049)。AD患者在选定CpG位点的甲基化率与对照者无差异。甲基化状态与临床特征、心理测试结果或mRNA表达均无相关性。
血液中的mRNA表达水平和甲基化状态似乎不能作为AD的生物标志物,或者所检测的CpG位点对基因表达或AD病理没有遗传学意义。然而AchEIs可能会改变mRNA表达。需要进一步研究以探索能够区分AD患者与对照者的血液生物标志物。