Abstract: Objective To explore the interaction between EBV infection and the single nucleotide polymorphism of apolipoprotein E gene and the development of Alzheimer's disease(AD).Methods DNA and serum was extracted from samples of peripheral blood cells from 18 AD patients and 20 normal elderly people.PCR amplification was used to detect the host Apo E gene,and then screened for genetic polymorphisms or mutations in Apo E gene by DNA direct sequencing.The serum was used to determine anti-EBV VCA Ig G、IgM antibodies by EL ISA.Results The HSV1 Ig G-positivity rate is far higher in AD patients than that of normals(P<0105);The ε4/4 and ε3/4 genotype in AD group were significantly higher than that in the controls(P<0.05).The association of Apo Eε4 with AD is significant in the HSV1 Ig G-positive patients(P=0.001,OR=1.809,4.976).Conclusion The finding suggested that the combination of anti-HSV1-positive in brain and carriage of an APO E-epsilon 4 allele is a strong risk factor for AD.