Abstract: OBJECTIVE To investigate the effect of herpes simplex virus-1 (HSV-1) infection on the expression of peripheral blood brain-derived neurotrophic factor (BDNF), neurotrophic factor (NGF) and platelet/endothelial cell adhesion molecule-1 (CD31) in patients with Alzheimer＇s disease (AD). METHODS The general clinical data of 86 patients with AD admitted to the Puyang People＇s Hospital between Aug. 2017 and Sep. 2020 were retrospectively analyzed. Patients with HSV-1 infection were included in the infection group (n=65), and those without HSV-1 infection were included in the control group (n=21), and the correlation between peripheral blood BDNF, NGF, CD31, BDNF, NGF, CD31, ApoE, tau, Aβ protein, and oxidative stress indicators in both groups was analyzed. RESULTS BDNF, NGF, and CD31 in the infection group were significantly lower than those in the control group (P<0.05). The levels of ApoE, tau, and Aβ protein in cerebrospinal fluid of the infection group were significantly higher than those in the control group (P<0.05). The levels of SOD, MDA, and NOS in the infection group were significantly higher than those in the control group (P<0.05). BDNF, NGF and CD31 were negatively correlated with ApoE, tau, Aβ protein, SOD, MDA and NOS (P<0.05). The infection group had significantly higher Cog-12 scores, and significantly lower MMSE and ADL scores, compared with the control group (P<0.05). CONCLUSION HSV-1 infection promoted the occurrence and development of AD, and decresed the levels of DNF, NGF and CD31 in cerebrospinal fluid, which might be associated with the alteration of ApoE, tau and Aβ proteins, and the induction of oxidative stress in patients with AD. Moreover, the cognitive function, mental state and quality of life of the patients was significantly reduced after infection.