ABSTRACT This study aimed to investigate the expression and mechanism of N- methyl -D- aspartate receptor 1 (NMDAR1) in the pathogenesis of Alzheimer disease (AD). Eighty adult Wistar rats were randomly divided into 4 groups (n=20 each) to receive an injection of 0, 5, 7 and 10 μl of 1 μg/μl amyloid-β 42 (Aβ1-42) in the hippocampus. Twenty rats in normal control group were injected with equal volume of saline. After 10 days, the hippocampus was isolated from 5 randomly selected rats in each group. The NMDAR1 protein and mRNA expression was determined by immunohistochemical staining and qRT-PCR. The aquaporin-1 (AQP-1) mRNA expression was also measured by qRT-PCR. We found that both NMDAR1 and AQP-1 expression in Aβ1-42 groups was increased in a dose-dependent manner. NMDAR1 and AQP-1 expression in 7 and 10 μl Aβ1-42 groups was significantly higher compared with 0 μl Aβ1-42 group (P <0.01). Further, the 10 μl Aβ1-42 group was randomly divided into 3 subgroups: AD-NMDA, AD-MK-801, and AD-Ctrl subgroup, which was given an intraperitoneal injection of NMDAR agonist NMDA, NMDAR antagonist MK-801 and saline, respectively. The relative APQ-1 expression in each subgroup was determined by qRT-PCR and Western blot analysis after 24 h. The AQP-1 expression was significantly decreased in AD-MK-801 group (P < 0.05), but was markedly increased in AD-NMDA group when compared with AD-Ctrl group (P <0.01). Our study suggested that expression abnormity of NMDAR1 is involved in the pathogenesis of AD. NMDAR1 might regulate the pathogenic process through stimulating the expression of AQP-1.