Wang Hao, Shi Lin, Luo Shimei, Luo Yishan, Xu Chunyan, Qiu Guozhen, Guo Qiwen, Chen Chunchun, Lu Taikun, Liu Kangding, Zhu Feiqi
Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin, China.
BrainNow Research Institute, Guangdong, China.
Front Neurol. 2024 Apr 2;15:1345705. doi: 10.3389/fneur.2024.1345705. eCollection 2024.
The ε4 allele of the apolipoprotein E gene (APOE4) is expressed abundantly in both the brain and peripheral circulation as a genetic risk factor for Alzheimer's disease (AD). Cerebral blood flow (CBF) dysfunction is an essential feature of AD, and the liver plays an important role in the pathogenesis of dementia. However, the associations of APOE4 with CBF and liver function markers in patients with cognitive impairment remains unclear. We aimed to evaluate the associations of APOE4 with CBF measured by arterial spin labeling (ASL) magnetic resonance imaging (MRI) and serum liver function markers in participants who were diagnosed with cognitive impairment.
Fourteen participants with AD and sixteen with amnestic mild cognitive impairment (MCI) were recruited. In addition to providing comprehensive clinical information, all patients underwent laboratory tests and MRI. All participants were divided into carriers and noncarriers of the ε4 allele, and T-tests and Mann-Whitney U tests were used to observe the differences between APOE4 carriers and noncarriers in CBF and liver function markers.
Regarding regional cerebral blood flow (rCBF), APOE4 carriers showed hyperperfusion in the bilateral occipital cortex, bilateral thalamus, and left precuneus and hypoperfusion in the right lateral temporal cortex when compared with noncarriers. Regarding serum liver function markers, bilirubin levels (including total, direct, and indirect) were lower in APOE4 carriers than in noncarriers.
APOE4 exerts a strong effect on CBF dysfunction by inheritance, representing a risk factor for AD. APOE4 may be related to bilirubin metabolism, potentially providing specific neural targets for the diagnosis and treatment of AD.
载脂蛋白E基因（APOE4）的ε4等位基因作为阿尔茨海默病（AD）的遗传风险因素，在大脑和外周循环中均大量表达。脑血流量（CBF）功能障碍是AD的一个基本特征，肝脏在痴呆症的发病机制中起重要作用。然而，APOE4与认知障碍患者的CBF和肝功能标志物之间的关联仍不清楚。我们旨在评估APOE4与通过动脉自旋标记（ASL）磁共振成像（MRI）测量的CBF以及在被诊断为认知障碍的参与者中的血清肝功能标志物之间的关联。
招募了14名AD患者和16名遗忘型轻度认知障碍（MCI）患者。除了提供全面的临床信息外，所有患者均接受了实验室检查和MRI检查。所有参与者被分为ε4等位基因携带者和非携带者，并使用T检验和曼-惠特尼U检验来观察APOE4携带者和非携带者在CBF和肝功能标志物方面的差异。
关于局部脑血流量（rCBF），与非携带者相比，APOE4携带者在双侧枕叶皮质、双侧丘脑和左侧楔前叶表现为血流灌注增加，而在右侧颞叶外侧皮质表现为血流灌注减少。关于血清肝功能标志物，APOE4携带者的胆红素水平（包括总胆红素、直接胆红素和间接胆红素）低于非携带者。
APOE4通过遗传对CBF功能障碍产生强烈影响，是AD的一个风险因素。APOE4可能与胆红素代谢有关，可能为AD的诊断和治疗提供特定的神经靶点。
