UK Dementia Research Institute at Cardiff University, Cardiff, United Kingdom.
UK Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom.
Neurobiol Aging. 2020 Sep;93:69-77. doi: 10.1016/j.neurobiolaging.2020.04.024. Epub 2020 Apr 30.
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.
阿尔茨海默病（AD）是一种具有重大遗传遗传性的破坏性神经退行性疾病。有几个基因与 AD 的发病有关，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，APOE 的作用在疾病进展过程中会随着年龄的变化而变化。在这里，我们旨在研究 APOE 以及 APOE 区域以外的其他变异对年轻和老年参与者患 AD 风险的影响。我们使用了来自阿尔茨海默病神经影像学倡议和英国生物库的数据集，并根据国际阿尔茨海默病基因组项目的最新遗传研究，计算了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，随着参与者年龄的增加而降低。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，年龄较大的个体的 AD 可能是由 APOE 区域以外的基因的累积效应引发的。
