Objective We aimed to evaluate the impact of interaction between APOE ε4 carrier status and body composition measurements on in-tra- and inter-regional functional connectivity (FC) in mild cognitive impairment (MCI) patients with Aβ deposition. Methods MCI patients with and without APOE ε4 allele (carrier, n=86; non-carrier, n=95) underwent neuropsychological battery, rest-ing-state functional magnetic resonance imaging scans, positron emission tomography scans with [18F]flutemetamol, and bioelectrical impedance analysis for measuring body composition. We employed a priori defined regions of interest to investigate the intra- and inter-network FC profiles of default mode network (DMN), central executive network (CEN), and salience network. Results There was a significant interaction of APOE ε4 carrier status with body fat mass index, visceral fat area, and waist-hip circum-ference ratio for inter-network FC between DMN and CEN, contributing higher fat-related body composition measurements in the APOE ε4 carrier with lower DMN-CEN FC. Conclusion The present results highlight the detrimental effect of APOE ε4 carrier status on the associations between the fat-related body composition measurements and FC in the MCI patients with Aβ accumulation.