Oh Sewook, Kim Sunghun, Kim Jun Pyo, Seo Sang Won, Park Bo-Yong, Park Hyunjin
Department of Electrical and Computer Engineering, Sungkyunkwan University, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea.
Center for Neuroscience Imaging Research, Institute for Basic Science, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea.
Geroscience. 2025 May 15. doi: 10.1007/s11357-025-01695-6.
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder, with its progression influenced by aberrant gene expression and alterations in the brain network topology. Although APOE has been extensively studied in relation to AD, the role of APOC1 remains relatively underexplored. This study investigated the impact of APOC1 on changes in cortical thickness (CTh) during conversion to AD in a longitudinal setting. Using a normative modeling approach, we examined changes in CTh in patients with mild cognitive impairment (MCI). The spatial patterns of CTh changes were then correlated with APOC1 mRNA expression levels. We estimated the time to conversion to AD and compared progression rates between the low and high APOC1 expression groups. Finally, mediation analysis was performed to assess the indirect effects of APOC1 expression on memory function via CTh changes. In patients with MCI and AD, reduced CTh was observed in the limbic and default mode regions, with a notable impact on the entorhinal cortex, parahippocampus, and fusiform gyrus when comparing baseline and follow-up measurements. The degree of change in CTh was significantly associated with APOC1 expression, with the paralimbic regions identified as particularly vulnerable. Furthermore, the high APOC1 expression group demonstrated more rapid conversion to AD than that observed in the low expression group. Mediation analysis indicated a trend suggesting that APOC1 expression indirectly affected memory and cognitive function through its influence on CTh. These results highlight the potential of APOC1 as an additional focus of AD research, offering insights into the genetic influences on AD pathology.
阿尔茨海默病（AD）是一种常见的神经退行性疾病，其进展受异常基因表达和脑网络拓扑结构改变的影响。尽管载脂蛋白E（APOE）已在AD相关研究中得到广泛探讨，但载脂蛋白C1（APOC1）的作用仍相对未被充分研究。本研究在纵向研究中调查了APOC1对向AD转化过程中皮质厚度（CTh）变化的影响。使用规范建模方法，我们检查了轻度认知障碍（MCI）患者的CTh变化。然后将CTh变化的空间模式与APOC1 mRNA表达水平相关联。我们估计了向AD转化的时间，并比较了低APOC1表达组和高APOC1表达组之间的进展速度。最后，进行中介分析以评估APOC1表达通过CTh变化对记忆功能的间接影响。在MCI和AD患者中，在边缘和默认模式区域观察到CTh降低，在比较基线和随访测量时，对内嗅皮质、海马旁回和梭状回有显著影响。CTh的变化程度与APOC1表达显著相关，边缘旁区域被确定为特别易受影响。此外，高APOC1表达组向AD的转化比低表达组更快。中介分析表明，APOC1表达可能通过其对CTh的影响间接影响记忆和认知功能。这些结果突出了APOC1作为AD研究额外重点的潜力，为AD病理学的遗传影响提供了见解。
