对轻度认知障碍和阿尔茨海默病所致痴呆患者血液进行全基因组甲基化测序可确定认知状态。
Whole genome methylation sequencing in blood from persons with mild cognitive impairment and dementia due to Alzheimer's disease identifies cognitive status.
作者信息
Madrid Andy, Papale Ligia A, Bergmann Phillip E, Breen Coleman, Clark Lindsay R, Asthana Sanjay, Johnson Sterling C, Keleş Sündüz, Hogan Kirk J, Alisch Reid S
机构信息
Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, USA.
Department of Statistics, University of Wisconsin, Medical Sciences Center, 1300 University Ave Room 1220, Madison, WI 53706 USA.
出版信息
bioRxiv. 2024 Sep 27:2024.09.26.615196. doi: 10.1101/2024.09.26.615196.
INTRODUCTION
Whole genome methylation sequencing (WGMS) in blood identifies differential DNA methylation in persons with late-onset dementia due to Alzheimer's disease (AD) but has not been tested in persons with mild cognitive impairment (MCI).
METHODS
We used WGMS to compare DNA methylation levels at 25,244,219 CpG loci in 382 blood samples from 99 persons with MCI, 109 with AD, and 174 who are cognitively unimpaired (CU).
RESULTS
WGMS identified 9,756 differentially methylated positions (DMPs) in persons with MCI, including 1,743 differentially methylated genes encoding proteins in biological pathways related to synapse organization, dendrite development, and ion transport. 447 DMPs exhibit progressively increasing or decreasing DNA methylation levels between CU, MCI, and AD that correspond to cognitive status.
DISCUSSION
WGMS identifies DMPs in known and newly detected genes in blood from persons with MCI and AD that support blood DNA methylation levels as candidate biomarkers of cognitive status.
引言
血液中的全基因组甲基化测序（WGMS）可识别阿尔茨海默病（AD）所致迟发性痴呆患者的差异DNA甲基化情况，但尚未在轻度认知障碍（MCI）患者中进行检测。
方法
我们使用WGMS比较了99例MCI患者、109例AD患者和174例认知未受损（CU）者的382份血液样本中25,244,219个CpG位点的DNA甲基化水平。
结果
WGMS在MCI患者中鉴定出9756个差异甲基化位点（DMP），其中包括1743个差异甲基化基因，这些基因编码与突触组织、树突发育和离子转运相关生物途径中的蛋白质。447个DMP在CU、MCI和AD之间呈现出与认知状态相对应的逐渐增加或减少的DNA甲基化水平。
讨论
WGMS在MCI和AD患者血液中的已知和新检测基因中鉴定出DMP，支持血液DNA甲基化水平作为认知状态的候选生物标志物。
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