Stening Eva, Persson Jonas, Eriksson Elias, Wahlund Lars-Olof, Zetterberg Henrik, Söderlund Hedvig
Department of Psychology, Uppsala University, Uppsala, Sweden.
Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
Behav Brain Res. 2017 May 30;326:256-264. doi: 10.1016/j.bbr.2017.03.013. Epub 2017 Mar 9.
Apolipoprotein E (APOE) ε4 has been associated with smaller hippocampal volumes in healthy aging, while findings in young adults are inconclusive. Previous studies have mostly used univariate methods, and without considering potential anterior/posterior differences. Here, we used a multivariate method, partial least squares, and assessed whole-brain structural covariance of the anterior (aHC) and posterior (pHC) hippocampus in young adults (n=97) as a function of APOE ε4 status and sex. Two significant patterns emerged: (1) specific structural covariance of the aHC with frontal regions, temporal and occipital areas in APOE ε4 women, whereas the volume of both the aHC and pHC in all other groups co-varied with frontal, parietal and cerebellar areas; and (2) opposite structural covariance of the pHC in ε4 carriers compared to the aHC in non-carriers, with the pHC of ε4 carriers covarying with parietal and frontal areas, and the aHC of ε4 non-carriers covarying with motor areas and the middle frontal gyrus. APOE ε4 has in young adults been associated with better episodic and spatial memory, functions involving the aHC and pHC, respectively. We found no associations between structural covariance and performance, suggesting that other factors underlie the performance differences seen between carriers and non-carriers. Our findings indicate that APOE ε4 carriers and non-carriers differ in hippocampal organization and that there are differences as a function of sex and hippocampal segment. They stress the need to consider the hippocampus as a heterogeneous structure, and highlight the benefits of multivariate methods in assessing group differences in the brain.
载脂蛋白E（APOE）ε4与健康衰老过程中较小的海马体积有关，而在年轻人中的研究结果尚无定论。以往的研究大多采用单变量方法，且未考虑潜在的前后差异。在此，我们使用多变量方法——偏最小二乘法，评估了年轻人（n = 97）中前海马（aHC）和后海马（pHC）的全脑结构协方差，将其作为APOE ε4状态和性别的函数。出现了两种显著模式：（1）在APOE ε4女性中，aHC与额叶区域、颞叶和枕叶区域存在特定的结构协方差，而在所有其他组中，aHC和pHC的体积均与额叶、顶叶和小脑区域协变；（2）与非携带者的aHC相比，ε4携带者的pHC存在相反的结构协方差，ε4携带者的pHC与顶叶和额叶区域协变，而ε4非携带者的aHC与运动区域和额中回协变。在年轻人中，APOE ε4分别与更好的情景记忆和空间记忆相关，这两种功能分别涉及aHC和pHC。我们未发现结构协方差与表现之间存在关联，这表明携带者和非携带者之间观察到的表现差异存在其他因素作为基础。我们的研究结果表明，APOE ε4携带者和非携带者在海马组织上存在差异，并且存在因性别和海马节段而异的差异。它们强调需要将海马视为一个异质性结构，并突出了多变量方法在评估大脑组间差异方面的益处。
