Gene-environment interactions in Alzheimer disease: the emerging role of epigenetics

被引:107
作者
Migliore, Lucia [1 ,2 ]
Coppede, Fabio [1 ]
机构
[1] Univ Pisa, Dept Translat Res & New Surg & Med Technol, Pisa, Italy
[2] Univ Hosp Pisa, Dept Lab Med, Pisa, Italy
基金
英国科研创新办公室;
关键词
GENOME-WIDE ASSOCIATION; ONE-CARBON METABOLISM; INCREASES PRESENILIN EXPRESSION; AMYLOID PRECURSOR PROTEIN; GAMMA-SECRETASE ACTIVITY; GLOBAL DNA METHYLATION; S-ADENOSYL METHIONINE; EARLY-LIFE EXPOSURE; LEAD PB ALTERS; OXIDATIVE STRESS;
D O I
10.1038/s41582-022-00714-w
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Most cases of Alzheimer disease (AD) have a complex aetiology, probably involving multiple genetic and environmental factors. In this Review, the authors discuss how various environmental AD risk factors could induce epigenetic modifications of key AD-associated genes and pathways. With the exception of a few monogenic forms, Alzheimer disease (AD) has a complex aetiology that is likely to involve multiple susceptibility genes and environmental factors. The role of environmental factors is difficult to determine and, until a few years ago, the molecular mechanisms underlying gene-environment (G x E) interactions in AD were largely unknown. Here, we review evidence that has emerged over the past two decades to explain how environmental factors, such as diet, lifestyle, alcohol, smoking and pollutants, might interact with the human genome. In particular, we discuss how various environmental AD risk factors can induce epigenetic modifications of key AD-related genes and pathways and consider how epigenetic mechanisms could contribute to the effects of oxidative stress on AD onset. Studies on early-life exposures are helping to uncover critical time windows of sensitivity to epigenetic influences from environmental factors, thereby laying the foundations for future primary preventative approaches. We conclude that epigenetic modifications need to be considered when assessing G x E interactions in AD.
引用
收藏
页码:643 / 660
页数:18
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