OBJECTIVE: To explore whether the vascular endothelial growth factor (VEGF) level changes the biological markers of Alzheimer's disease (AD) and discover the relationship between VEGF and the brain aging. PATIENTS AND METHODS: The neuroimaging and neuropsychological results on Alzheimer's disease neuroimaging program (ADNI) were analyzed as biomarkers. Participants were all recruited from ADNI including cognitive ability (n= 90), mild cognitive impairment (n= 130) and AD (n= 59). The relationship between VEGF level in cerebrospinal fluid (CSF) and hippocampal volume, episodic memory and executive ability was compared laterally and longitudinally, in order to evaluate whether VEGF was effective. Moreover, the correlation between VEGF levels in CSF and the results of brain aging was detected and evaluated, so as to detect the level of VEGF in CSF and the continuous determination of the relationship with AD biomarkers (A beta 42, total t protein). RESULTS: The general linear model and the multiple regression research indicated that the VEGF in CSF was related to the brain aging (hippocampal volume, episodic memory and executive ability). The interaction between AD biomarkers (CSF amyloid beta (A beta-42) and total t protein) and VEGF promoted AD biomarkers to enhance the effect of VEGF on the brain aging. The VEGF correlated with the baseline hippocampal volume (p = 0.009), longitudinal hippocampal atrophy (p = 0.010), longitudinal memory decline (p < 0.0001) and longitudinal executive capacity decline (p = 0.003). In the prediction of longitudinal hippocampal atrophy (p < 0.0001) memory loss (p = 0.010) and implementation capacity (p = 0.0002), the VEGF and t protein interacted with each other. In the prediction of longitudinal memory loss (p = 0.010), the VEGF interacted with amyloid-beta 4. CONCLUSIONS: The elevated VEGF in CSF is associated with the brain aging. When AD biomarkers were elevated, the VEGF had the strongest neuro-protective effect. Moreover, in the positive AD biomarkers, especially the individual t protein, the protective effect of VEGF was the strongest. In the prediction of longitudinal changes in the hippocampal volume, the memory and the executive ability, the interactions of VEGF and t protein were observed. VEGF and A beta-42 also interacted with each other in case of longitudinal changes in the memory performance.