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

doi:10.1002/alz.13775

APOE ε4 is associated with decreased synaptic density in cognitively impaired participants

Alzheimers Dement. 2024 Mar 13. doi: 10.1002/alz.13775. Online ahead of print.

Authors

Kun He¹, Binyin Li^{2

3}, Jie Wang¹, Ying Wang⁴, Zhiwen You⁵, Xing Chen⁵, Haijuan Chen², Junpeng Li¹, Qi Huang¹, Qihao Guo⁴, Yiyun Henry Huang⁶, Yihui Guan¹, Kewei Chen⁷, Jun Zhao⁵, Yulei Deng^{2

3}, Fang Xie^{1

8}

Affiliations

¹ Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.
² Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Clinical Neuroscience Center, Ruijin Hospital LuWan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Department of Gerontology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
⁵ Department of Nuclear Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
⁶ PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, USA.
⁷ Banner Alzheimer Institute, Arizona State University, University of Arizona and Arizona Alzheimer's Consortium, Phoenix, USA.
⁸ State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.

PMID: 38477490
DOI: 10.1002/alz.13775

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 ¹⁸ F-florbetapir and synaptic density PET with ¹⁸ 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.

Keywords: APOE ε4; Alzheimer's disease biomarker; female risk; hippocampal subfields; synaptic density.

Grants and funding

P30 AG072980/AG/NIA NIH HHS/United States