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普通人群中微小RNA与阿尔茨海默病遗传易感性对记忆轨迹的相互作用。

The interplay between micro RNAs and genetic liability to Alzheimer's Disease on memory trajectories in the general population.

作者信息

Van der Auwera Sandra, Garvert Linda, Ameling Sabine, Völzke Henry, Nauck Matthias, Völker Uwe, Grabe Hans J

机构信息

Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; German Center for Neurodegenerative Diseases DZNE, Site Rostock/Greifswald, Greifswald, Germany.

Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.

出版信息

Psychiatry Res. 2023 May;323:115141. doi: 10.1016/j.psychres.2023.115141. Epub 2023 Mar 2.

Abstract

Deficits in cognitive function and memory are common early symptoms of neurodegenerative disorders, such as Alzheimer's Disease (AD). Several studies have discussed micro RNAs (miRNAs) as potential epigenetic early detection biomarkers. In a longitudinal general population sample (n = 548) from the Study of Health in Pomerania, we analyzed the associations between 167 baseline miRNA levels and changes in verbal memory scores with a mean follow-up time of 7.4 years. We additionally assessed the impact of an individual's genetic liability for AD on verbal memory scores in n = 2,334 subjects and a possible interactions between epigenetic and genetic markers. Results revealed two miRNAs associated with changes in immediate verbal memory over time. In interaction analyses between miRNAs and a polygenic risk score for AD, five miRNAs showed a significant interaction effect on changes in verbal memory. All of these miRNAs have previously been identified in the context of AD, neurodegeneration or cognition. Our study provides candidate miRNAs for a decline in verbal memory as an early symptom of neurodegeneration and AD. Further experimental studies are needed to verify the diagnostic value of these miRNA markers in the prodromal stage of AD.

摘要

认知功能和记忆缺陷是神经退行性疾病(如阿尔茨海默病,AD)常见的早期症状。多项研究探讨了微小RNA(miRNA)作为潜在的表观遗传早期检测生物标志物。在波美拉尼亚健康研究的纵向普通人群样本(n = 548)中,我们分析了167种基线miRNA水平与言语记忆分数变化之间的关联,平均随访时间为7.4年。我们还评估了n = 2334名受试者中个体患AD的遗传易感性对言语记忆分数的影响,以及表观遗传和遗传标记之间可能的相互作用。结果显示,有两种miRNA与即时言语记忆随时间的变化相关。在miRNA与AD多基因风险评分的交互分析中,五种miRNA对言语记忆变化显示出显著的交互作用。所有这些miRNA此前已在AD、神经退行性变或认知的背景下被鉴定出来。我们的研究为言语记忆下降这一神经退行性变和AD的早期症状提供了候选miRNA。需要进一步的实验研究来验证这些miRNA标记物在AD前驱期的诊断价值。

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