Objective To investigate the effects of apolipoprotein E(APOE)ε4 allele on β-amy-loid(Aβ)deposition in subcortical structures and functional connectivity(FC)between brain regions in patients with Alzheimer's disease(AD).Methods Forty-three patients with probable mild/moderate AD were prospectively enrolled from the First Medical Centre,Chinese PLA General Hospital between January 2023 and October 2023,including 23 APOE ε4+patients(12 males and 11 females,age(74.8±8.4)years),20 APOE ε4-patients(14 males and 6 females,age(77.6±8.9)years)and 20 normal cognitive volunteers(NC)(15 males and 5 females,age(75.3±6.2)years).All subjects underwent 11C-Pittsburgh compound B(PIB)PET/MR brain imaging.The differences of gray matter volume(GMV)in subcortical structures(hippocampus,amygdala)among the three groups were analyzed by one-way analysis of variance and least significant difference(LSD)t test.Independent-sample t test and Pearson correlation analysis were used to analyze difference in Aβ deposition between APOE ε4+patients and APOE ε4-patients,and the correlation between subcortical structure and brain FC.Results The GMV of bilateral amygdala between NC group and APOE ε4+gene carrier group,and between APOE ε4+and APOE ε4-gene carrier groups were significantly different(F=6.43,P=0.002;P values:0.002,0.003).Significant difference of GMV was observed in the bilateral hippocampus among three groups(F=5.34,P=0.030).Abnormal PIB uptake was detected in both the hippocampus and amygdala of both APOE ε4+and APOE ε4-gene carrier groups,with a more pronounced effect observed in the APOE ε4+group(t values:3.14,2.19,P values:0.032,0.009).Taking the hippocampus as the seed point,there was no obvious abnormality in the whole brain con-nectivity map among APOE ε4+,APOE ε4-carriers and NC groups.With the amygdala as the seed point,the whole brain connectivity in the APOE ε4+gene carrier group was significantly reduced,and the connectivity between the amygdala and the cingulate gyrus,parietal lobe and temporal lobe was significantly reduced in the APOE ε4+gene carrier group compared with NC group,while the connectivity between the amygdala and the whole brain was not significantly reduced in the APOE ε4-gene carrier group.Aβ deposition in amygdala was positively correlated with FC coefficients of frontal brain regions,gyrus rectus,right middle occipital gyrus and left temporal lobe(r values:0.56-0.70,all P<0.05).Conclusion APOE influences GMV and Aβdeposition of hippocampus and amygdala,and FC of amygdala,and may be involved in the pathological mechanism of cognitive impairment.