Tatsuo Mano, Department of Neurology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan, Email:
J Prev Alzheimers Dis. 2021;8(4):477-482. doi: 10.14283/jpad.2021.31.
Recent biomarker studies demonstrated that the central nervous system (CNS) environment can be observed from peripherally-derived samples. In a previous study, we demonstrated significant hypomethylation of the BRCA1 promoter region in neuronal cells from post-mortem brains of Alzheimer's disease patients through neuron-specific methylome analysis. Thus, we investigate the methylation changes in the BRCA1 promoter region in the blood samples.
To analyze the methylation level of the BRCA1 promoter in peripheral blood from AD patients and normal controls.
DESIGN, SETTING, PARTICIPANTS: Genomic DNA samples from peripheral blood were obtained from the J-ADNI repository, and their biomarker data were obtained J-ADNI from the National Bioscience Database Center. Genomic DNA samples from an independent cohort for validation was obtained from Niigata University Hospital (Niigata, Japan). Amyloid positivity was defied by visual inspection of amyloid PET or a CSF Aβ42 value ≤ 333 pg/mL at the baseline.
Methylation level of the BRCA1 promoter was analyzed by pyrosequencing.
Compared to normal controls, methylation of the BRCA1 promoter in AD patients was not significantly changed; however, in AD patients, it showed a positive correlation with AD risk factors.
Our data confirmed the importance of cell-type specific methylome analysis and also suggested that environmental changes in the CNS can be detected by observing the peripheral blood, implying that the peripheral BRCA1 methylation level can be a surrogate for AD.
最近的生物标志物研究表明，中枢神经系统 (CNS) 环境可以从外周来源的样本中观察到。在之前的一项研究中，我们通过神经元特异性甲基组分析，证明了阿尔茨海默病患者死后大脑神经元中 BRCA1 启动子区域的显著低甲基化。因此，我们研究了血液样本中 BRCA1 启动子区域的甲基化变化。
分析 AD 患者和正常对照者外周血中 BRCA1 启动子的甲基化水平。
设计、地点、参与者：从 J-ADNI 存储库中获得外周血的基因组 DNA 样本，并从国家生物科学数据库中心获得 J-ADNI 的生物标志物数据。用于验证的独立队列的基因组 DNA 样本来自新泻大学医院（日本新泻）。淀粉样蛋白阳性通过淀粉样蛋白 PET 的视觉检查或基线时 CSF Aβ42 值≤333 pg/mL 来定义。
通过焦磷酸测序分析 BRCA1 启动子的甲基化水平。
与正常对照组相比，AD 患者的 BRCA1 启动子甲基化没有明显变化；然而，在 AD 患者中，它与 AD 风险因素呈正相关。
我们的数据证实了细胞类型特异性甲基组分析的重要性，并表明可以通过观察外周血来检测 CNS 的环境变化，这意味着外周 BRCA1 甲基化水平可以作为 AD 的替代标志物。
