Abstract: Objective To explore the correlation between aquaporin 4 (AQP4) and Alzheimer's disease (AD). Methods Agilent expression profile chip was used to screen the gene expression differences through the comparison between SAMP8 and SAMR1 after total RNA of brain tissue being extracted out, then Real-Time PCR technology and indirect immunofluorescence assay were applied for identification. Results Totally 804 genes related to dementia were selected, among which the number of up-regulated genes was 521 and down-regulated genes was 283. The biological function and pathways of the related genes were searched in GeneBank, then six genes were found to be closely related to AD:Herc6, Lyst, Nkain1, Aqp4, Uch13, Slc9a8. The fold change of Aqp4 was 6.26 with P< 0.001. The Real-time PCR of the Aqp4 gene showed that the expression quantity in SAMP8 group was higher than that in SAMR1 group (P=0.037 6), and the immunofluorescence assay showed that the expression of Aqp4 in SAMP8 also increased. Conclusion Increased Aqp4 expression is related to the increased need for Aβ clearance in SAMP8 rats which has astrocytes compensatory proliferation.