Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Psychiatry, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
J Alzheimers Dis. 2022;89(3):1003-1016. doi: 10.3233/JAD-220427.
There has been renewed interest in the deteriorating effects of sub-threshold amyloid-β (Aβ) accumulation in Alzheimer's disease (AD). Despite evidence suggesting a synergistic interaction between the APOE ɛ4 allele and Aβ deposition in neurodegeneration, few studies have investigated the modulatory role of this allele in sub-threshold Aβ deposition during the preclinical phase.
We aimed to explore the differential effect of the APOE ɛ4 carrier status on the association between sub-threshold Aβ deposition, cortical volume, and cognitive performance in cognitively normal older adults (CN).
A total of 112 CN with sub-threshold Aβ deposition was included in the study. Participants underwent structural magnetic resonance imaging, [18F] flutemetamol PET-CT, and a neuropsychological battery. Potential interactions between APOE ɛ4 carrier status, Aβ accumulation, and cognitive function for cortical volume were assessed with whole-brain voxel-wise analysis.
We found that greater cortical volume was observed with higher regional Aβ deposition in the APOE ɛ4 carriers, which could be attributed to an interaction between the APOE ɛ4 carrier status and regional Aβ deposition in the posterior cingulate cortex/precuneus. Finally, the APOE ɛ4 carrier status-neuropsychological test score interaction demonstrated a significant effect on the gray matter volume of the left middle occipital gyrus.
There might be a compensatory response to initiating Aβ in APOE ɛ4 carriers during the earliest AD stage. Despite its exploratory nature, this study offers some insight into recent interests concerning probabilistic AD modeling, focusing on the modulating role of the APOE ɛ4 carrier status during the preclinical period.
人们对阿尔茨海默病（AD）中阈下淀粉样蛋白-β（Aβ）积累的恶化影响重新产生了兴趣。尽管有证据表明 APOE ε4 等位基因与神经退行性变中的 Aβ 沉积之间存在协同相互作用，但很少有研究调查该等位基因在临床前阶段阈下 Aβ 沉积中的调节作用。
我们旨在探讨 APOE ε4 携带状态对认知正常老年人（CN）中阈下 Aβ 沉积、皮质体积和认知表现之间关联的差异影响。
本研究共纳入 112 名具有阈下 Aβ 沉积的认知正常老年人。参与者接受了结构磁共振成像、[18F] flutemetamol PET-CT 和神经心理学测试。使用全脑体素分析评估 APOE ε4 携带状态、Aβ 积累和认知功能之间的潜在相互作用。
我们发现，在 APOE ε4 携带者中，随着区域 Aβ 沉积的增加，皮质体积越大，这可能归因于 APOE ε4 携带状态与后扣带回/楔前叶的区域 Aβ 沉积之间的相互作用。最后，APOE ε4 携带状态-神经心理学测试分数的相互作用对左侧中枕叶的灰质体积有显著影响。
在 AD 的最早阶段，APOE ε4 携带者中可能存在启动 Aβ 的代偿反应。尽管这是一项探索性研究，但本研究为最近关于概率 AD 建模的研究提供了一些启示，重点关注了 APOE ε4 携带状态在临床前阶段的调节作用。
