No effect of apolipoprotein E polymorphism on MRI brain activity during movie watching.

Brain and neuroscience advances Pub Date : 2025-01-31 eCollection Date: 2025-01-01 DOI:10.1177/23982128251314577
Petar P Raykov, Jessica Daly, Simon E Fisher, Else Eising, Linda Geerligs, Chris M Bird
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Abstract

Apolipoprotein E ε4 is a major genetic risk factor for Alzheimer's disease, and some apolipoprotein E ε4 carriers show Alzheimer's disease-related neuropathology many years before cognitive changes are apparent. Therefore, studying healthy apolipoprotein E genotyped individuals offers an opportunity to investigate the earliest changes in brain measures that may signal the presence of disease-related processes. For example, subtle changes in functional magnetic resonance imaging functional connectivity, particularly within the default mode network, have been described when comparing healthy ε4 carriers to ε3 carriers. Similarly, very mild impairments of episodic memory have also been documented in healthy apolipoprotein E ε4 carriers. Here, we use a naturalistic activity (movie watching), and a marker of episodic memory encoding (transient changes in functional magnetic resonance imaging activity and functional connectivity around so-called 'event boundaries'), to investigate potential phenotype differences associated with the apolipoprotein E ε4 genotype in a large sample of healthy adults. Using Bayes factor analyses, we found strong evidence against existence of differences associated with apolipoprotein E allelic status. Similarly, we did not find apolipoprotein E-associated differences when we ran exploratory analyses examining: functional system segregation across the whole brain, and connectivity within the default mode network. We conclude that apolipoprotein E genotype has little or no effect on how ongoing experiences are processed in healthy adults. The mild phenotype differences observed in some studies may reflect early effects of Alzheimer's disease-related pathology in apolipoprotein E ε4 carriers.

载脂蛋白E多态性对看电影时MRI脑活动无影响。
载脂蛋白E ε4是阿尔茨海默病的主要遗传危险因素,一些载脂蛋白E ε4携带者在认知变化明显前多年就表现出阿尔茨海默病相关的神经病理。因此,研究健康的载脂蛋白E基因型个体提供了一个机会来研究大脑测量的早期变化,这些变化可能表明疾病相关过程的存在。例如,在比较健康的ε4载流子和ε3载流子时,已经描述了功能磁共振成像功能连通性的细微变化,特别是在默认模式网络内。同样,健康的载脂蛋白E ε4携带者也有非常轻微的情景记忆障碍。在这里,我们使用自然活动(看电影)和情景记忆编码标记(功能性磁共振成像活动的短暂变化和所谓的“事件边界”周围的功能连接)来研究大量健康成年人中与载脂蛋白E ε4基因型相关的潜在表型差异。使用贝叶斯因子分析,我们发现了强有力的证据反对存在与载脂蛋白E等位基因状态相关的差异。同样,当我们进行探索性分析检查时,我们没有发现载脂蛋白e相关的差异:整个大脑的功能系统分离,以及默认模式网络内的连接。我们的结论是,载脂蛋白E基因型对健康成人如何处理正在进行的经历影响很小或没有影响。在一些研究中观察到的轻微表型差异可能反映了载脂蛋白E ε4携带者阿尔茨海默病相关病理的早期影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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