Muñoz-Neira Carlos, Zeng Jianmin, Kucikova Ludmila, Huang Weijie, Xiong Xiong, Muniz-Terrera Graciela, Ritchie Craig, O'Brien John T, Su Li
Artificial Intelligence & Computational Neuroscience Group (AICN Group), Sheffield Institute for Translational Neuroscience (SITraN), Division of Neuroscience, School of Medicine and Population Health, Faculty of Health, University of Sheffield, Sheffield S10 2HQ, UK.
Old Age Psychiatry Research Group (OAP Group), Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SZ, UK.
J Clin Med. 2024 Sep 3;13(17):5228. doi: 10.3390/jcm13175228.
: The pathophysiology of Alzheimer's disease (AD) may begin developing years or even decades prior to the manifestation of its first symptoms. The APOE ε4 genotype is a prominent genetic risk for AD that has been found to be associated with brain changes across the lifespan since early adulthood. Thus, studying brain changes that may occur in young adults with an APOE ε4 status is highly relevant. : Examine potential differences in grey matter (GM) and functional connectivity (FC) in brains of cognitively healthy young APOE ε4 carriers and non-carriers, denoted here as ε4(+) and ε4(-), respectively. : Three Tesla magnetic resonance imaging (MRI) brain scans were acquired from cognitively healthy young participants aged approximately 20 years (n = 151). Voxel-based morphometry (VBM) analysis was employed to identify potential structural differences in GM between ε4(+) and ε4(-). In a subsequent seed-based connectivity (SBC) analysis, brain regions that structurally differed in the VBM analysis were considered as seeds and correlated with all the remaining voxels across the brains to then measure the differences in FC between groups. : The VBM analysis suggested that ε4(+) (n = 28) had greater GM densities relative to ε4(-) (n = 123) in the left hippocampus and the left posterior insula (p < 0.001). However, the effect did not survive the correction for multiple comparisons, suggesting minimal structural differences in this age range. In contrast, the SBC analysis indicated that ε4(+) exhibited significantly decreased FC between the left hippocampus and areas of the left middle temporal gyrus (n = 27) compared to ε4(-) (n = 102). These results remained significant after multiple comparisons (p < 0.05). Lastly, no statistically significant differences in FC between groups were observed for the left insular seed (p > 0.05). : These results suggest early structural and functional brain changes associated with the APOE ε4 genotype on young adults. Yet, they must be cautiously interpreted and contrasted with both older adults with genetic risk for AD and patients diagnosed with AD.
阿尔茨海默病（AD）的病理生理学可能在其首次症状出现前数年甚至数十年就开始发展。APOE ε4基因型是AD的一个显著遗传风险因素，自成年早期以来，已发现其与整个生命周期的大脑变化有关。因此，研究具有APOE ε4状态的年轻人可能出现的大脑变化具有高度相关性。：检查认知健康的年轻APOE ε4携带者和非携带者（此处分别表示为ε4(+)和ε4(-)）大脑中灰质（GM）和功能连接（FC）的潜在差异。：对年龄约20岁的认知健康年轻参与者（n = 151）进行了三次3特斯拉磁共振成像（MRI）脑部扫描。基于体素的形态计量学（VBM）分析用于识别ε4(+)和ε4(-)之间GM的潜在结构差异。在随后的基于种子的连接性（SBC）分析中，将VBM分析中结构不同的脑区视为种子，并与大脑中所有其余体素进行相关性分析，以测量组间FC的差异。：VBM分析表明，相对于ε4(-)（n = 123），ε4(+)（n = 28）在左侧海马体和左侧后岛叶的GM密度更高（p < 0.001）。然而，该效应在多重比较校正后未保留，表明在这个年龄范围内结构差异最小。相比之下，SBC分析表明，与ε4(-)（n = 102）相比，ε4(+)在左侧海马体和左侧颞中回区域之间的FC显著降低。经过多重比较后，这些结果仍然显著（p < 0.05）。最后，对于左侧岛叶种子，未观察到组间FC的统计学显著差异（p > 0.05）。：这些结果表明，与APOE ε4基因型相关的大脑早期结构和功能变化发生在年轻人身上。然而，必须谨慎解释这些结果，并与具有AD遗传风险的老年人以及被诊断为AD的患者进行对比。
