Alzheimer's disease (AD) is a devastating neurodegenerative condition with significant genetic heritability. Several genes have been implicated in the onset of AD with the apolipoprotein E (APOE) gene being the strongest single genetic risk loci. Evidence suggests that the effect of APOE alters with age during disease progression. Here, we aim to investigate the impact of APOE and other variants outside the APOE region on AD risk in younger and older participants. Using data from both the Alzheimer's Disease Neuroimaging Initiative and the UK Biobank, we computed the polygenic risk score of each individual informed by the latest genetic study from the International Genomics of Alzheimer's Project. Our analysis showed that the effect of APOE on the disease risk is greater in younger participants and reduces as participants' age increases. Our findings indicate the increased impact of polygenic risk score as participants' age increases. Therefore, AD in older individuals can potentially be triggered by the cumulative effect of genes which are outside the APOE region.

中文翻译：

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APOE和多基因成分对阿尔茨海默病的年龄依赖性影响

阿尔茨海默病 (AD) 是一种具有显着遗传遗传性的破坏性神经退行性疾病。一些基因与 AD 的发病有关，其中载脂蛋白 E (APOE) 基因是最强的单一遗传风险基因座。有证据表明，在疾病进展过程中，APOE 的作用会随着年龄的增长而变化。在这里，我们旨在调查 APOE 和 APOE 区域以外的其他变体对年轻和年长参与者 AD 风险的影响。利用阿尔茨海默病神经影像学计划和英国生物银行的数据，我们计算了国际阿尔茨海默病基因组学项目最新基因研究所获悉的每个个体的多基因风险评分。我们的分析表明，APOE 对疾病风险的影响在年轻参与者中更大，并且随着参与者的 年龄增加。我们的研究结果表明，随着参与者年龄的增加，多基因风险评分的影响会增加。因此，老年人的 AD 可能由 APOE 区域之外的基因的累积效应触发。