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In our study, NAC co-treatment not only ameliorated the impaired performance in NOR, Y maze, and MWM in chronic ethanol-exposed APP/PS1 mice, but also significantly alleviated the neuroinflammation, downregulated TNF- protein level and restored SYP, PSD95 and BDNF protein levels in the hippocampus of ethanol-exposed APP/PS1 mice, further suggesting the critical role of chronic ethanol exposure mediated oxidative stress and neuroinflammatory damage in AD pathology and the cognitive behavioral impairments