载脂蛋白 E ε4 与认知障碍参与者的突触密度降低有关。
APOE ε4 is associated with decreased synaptic density in cognitively impaired participants.
机构信息
Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.
Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
出版信息
Alzheimers Dement. 2024 May;20(5):3157-3166. doi: 10.1002/alz.13775. Epub 2024 Mar 13.
INTRODUCTION
We aimed to investigate the effect of apolipoprotein E4 (APOE) ε4 on synaptic density in cognitively impaired (CI) participants.
METHODS
One hundred ten CI participants underwent amyloid positron emission tomography (PET) with F-florbetapir and synaptic density PET with F-SynVesT-1. We evaluated the influence of APOE ε4 allele on synaptic density and investigated the effects of ε4 genotype on the associations of synaptic density with Alzheimer's disease (AD) biomarkers. The mediation effects of AD biomarkers on ε4-associated synaptic density loss were analyzed.
RESULTS
Compared with non-carriers, APOE ε4 allele carriers exhibited significant synaptic loss in the medial temporal lobe. Amyloid beta (Aβ) and tau pathology mediated the effects of APOE ε4 on synaptic density to different extents. The associations between synaptic density and tau pathology were regulated by the APOE ε4 genotype.
DISCUSSION
The APOE ε4 allele was associated with decreased synaptic density in CI individuals and may be driven by AD biomarkers.
简介
我们旨在研究载脂蛋白 E4 (APOE) ε4 对认知障碍 (CI) 参与者突触密度的影响。
方法
110 名认知障碍参与者接受了 F-氟比他滨正电子发射断层扫描 (PET) 和 F-SynVesT-1 突触密度 PET。我们评估了 APOE ε4 等位基因对突触密度的影响，并研究了 ε4 基因型对突触密度与阿尔茨海默病 (AD) 生物标志物相关性的影响。分析了 AD 生物标志物对与 ε4 相关的突触密度丧失的中介效应。
结果
与非携带者相比，APOE ε4 等位基因携带者的内侧颞叶突触密度显著下降。淀粉样蛋白β (Aβ) 和 tau 病理学在不同程度上介导了 APOE ε4 对突触密度的影响。突触密度与 tau 病理学之间的关联受 APOE ε4 基因型的调节。
讨论
APOE ε4 等位基因与 CI 个体中突触密度降低有关，可能是由 AD 生物标志物驱动的。
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