APOE ε4 is associated with decreased synaptic density in cognitively impaired participants
Kun He, Binyin Li, Jie Wang, Ying Wang, Zhiwen You, Xing Chen, Haijuan Chen, Junpeng Li, Qi Huang, Qihao Guo, Yiyun Henry Huang, Yihui Guan, Kewei Chen, Jun Zhao, Yulei Deng, Fang Xie- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
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 18F‐florbetapir and synaptic density PET with 18F‐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.