Objective: To explore the intrinsic mechanism of Nrf2 improving cognitive dysfunction in Alzheimer's disease (AD) through antioxidant effects. Methods: APP/PS1 mice were used as AD model mice, and the Nrf2 downregulated mouse model was established by injecting lentivirus into the hippocampus. Morris water maze test was used to evaluate the learning and memory ability of mice, and real-time quantitative polymerase chain reaction (RT-PCR) was used to detect the levels of Nrf2 mRNA. Western blotting was used to detect the expression of Nrf2, GCLC, and Aβ protein. Immunohistochemistry was used to observe the expression of Aβ protein in hippocampal tissue. Immunofluorescence was used to observe the expression of MAP2 in hippocampal tissue. Transmission electron microscopy was used to observe the structure of neural synapses. Results: Compared with the control group mice, the levels of Nrf2, GCLC protein and MAP2 in AD model mice were decreased, Aβ protein deposition increased, synaptic damage and cognitive impairment were aggravated (P < 0.05). Lentivirus-induced Nrf2 downregulation downregulated GCLC protein expression, decreased MAP2 levels, and aggravates Aβ protein deposition, synaptic damage and cognitive impairment (P < 0.05). Conclusion: Lentivirus-downregulated Nrf2 aggravated the oxidative stress response by downregulating GCLC, aggravates Aβ protein deposition and synaptic damage, and further aggravated the cognitive dysfunction of AD.