载脂蛋白 E 基因的 DNA 甲基化在路易体痴呆中发生改变。
APOE DNA methylation is altered in Lewy body dementia.
机构信息
Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.
Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.
出版信息
Alzheimers Dement. 2018 Jul;14(7):889-894. doi: 10.1016/j.jalz.2018.02.005. Epub 2018 Mar 12.
INTRODUCTION
Inheritance of the ε4 allele of apolipoprotein E (APOE) increases a person's risk of developing both Alzheimer's disease (AD) and Lewy body dementia (LBD), yet the underlying mechanisms behind this risk are incompletely understood. The recent identification of reduced APOE DNA methylation in AD postmortem brains prompted this study to investigate APOE methylation in LBD.
METHODS
Genomic DNA from postmortem brain tissues (frontal lobe and cerebellum) of neuropathological pure (np) controls and npAD, LBD + AD, and npLBD subjects were bisulfite pyrosequenced. DNA methylation levels of two APOE subregions were then compared for these groups.
RESULTS
APOE DNA methylation was significantly reduced in npLBD compared with np controls, and methylation levels were lowest in the LBD + AD group.
DISCUSSION
Given that npLBD and npAD postmortem brains shared a similar reduction in APOE methylation, it is possible that an aberrant epigenetic change in APOE is linked to risk for both diseases.
简介
载脂蛋白 E (APOE) 的 ε4 等位基因的遗传增加了一个人患阿尔茨海默病 (AD) 和路易体痴呆症 (LBD) 的风险，但这种风险背后的潜在机制尚不完全清楚。最近在 AD 尸检大脑中发现 APOE DNA 甲基化减少，促使本研究调查 LBD 中的 APOE 甲基化。
方法
对神经病理学纯 (np) 对照组和 npAD、LBD+AD 和 npLBD 受试者的死后脑组织（额叶和小脑）中的基因组 DNA 进行亚硫酸氢盐焦磷酸测序。然后比较这些组中两个 APOE 亚区的 DNA 甲基化水平。
结果
与 np 对照组相比，npLBD 中的 APOE DNA 甲基化显著降低，而在 LBD+AD 组中甲基化水平最低。
讨论
鉴于 npLBD 和 npAD 尸检大脑中 APOE 甲基化减少相似，APOE 中异常的表观遗传变化可能与两种疾病的风险相关。
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