Dowell Nicholas G, Evans Simon L, Tofts Paul S, King Sarah L, Tabet Naji, Rusted Jennifer M
Brighton and Sussex Medical School, Brighton, UK.
School of Psychology, University of Sussex, Brighton, UK.
NMR Biomed. 2016 May;29(5):614-24. doi: 10.1002/nbm.3502. Epub 2016 Feb 29.
The presence of the e4 allele of the apolipoprotein E (APOE) gene is the best-known genetic risk factor for Alzheimer's disease. In this study, we investigated the link between functional and behavioural differences and regional brain volume and cortical thickness differences in those who carry the e4 allele (e4+) and those who only carry the e3 allele (e3/e3). We studied these genotype populations in two age groups: a young group (average age, 21 years) and a mid-age group (average age, 50 years). High-resolution T1 -weighted MRI scans were analysed with Freesurfer to measure regional white matter brain volume and cortical thickness differences between genotype groups at each age. These data were correlated with behavioural findings in the same cohort. Resting-state MRI was also conducted to identify differences in underlying brain functional connectivity. We found that there was a positive correlation between the thickness of the parahippocampal cortex in young e4+ individuals and performance on an episodic memory task. Young e4+ individuals also showed a positive correlation between white matter volume in the left anterior cingulate and performance on a covert attention task. At mid-age, e4+ individuals had structural differences relative to e3/e3 individuals in these areas: the parahippocampal cortex was thicker and white matter volume in the left anterior cingulate was greater than in e3/e3 individuals. We discuss the possibility that an over-engagement with these regions by e4+ individuals in youth may have a neurogenic effect that is observable later in life. The cuneus appears to be an important region for APOE-driven differences in the brain, with greater functional connectivity among young e3/e3 individuals and greater white matter volume in young e4+ individuals.
载脂蛋白E（APOE）基因的e4等位基因是阿尔茨海默病最著名的遗传风险因素。在本研究中，我们调查了携带e4等位基因（e4+）的个体与仅携带e3等位基因（e3/e3）的个体在功能和行为差异与脑区体积及皮质厚度差异之间的联系。我们在两个年龄组中研究了这些基因型人群：一个年轻组（平均年龄21岁）和一个中年组（平均年龄50岁）。使用Freesurfer分析高分辨率T1加权MRI扫描，以测量各年龄组基因型之间的脑区白质体积和皮质厚度差异。这些数据与同一队列中的行为学结果相关。还进行了静息态MRI以识别潜在脑功能连接的差异。我们发现，年轻e4+个体的海马旁皮质厚度与情景记忆任务表现之间存在正相关。年轻e4+个体还显示左前扣带回白质体积与隐蔽注意任务表现之间存在正相关。在中年时，e4+个体在这些区域相对于e3/e3个体存在结构差异：海马旁皮质更厚，左前扣带回白质体积大于e3/e3个体。我们讨论了e4+个体在年轻时过度使用这些区域可能产生一种在生命后期可观察到的神经源性效应的可能性。楔叶似乎是APOE驱动的脑差异的一个重要区域，年轻e3/e3个体之间的功能连接更强，而年轻e4+个体的白质体积更大。
