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

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.