Cover Story：The formation of plaques by the deposition of amyloid-β (Aβ) in the brain is a hallmark of Alzheimer’s disease (AD). Transgenic mouse models based on amyloid- β precursor protein (AβPP) exhibited accelerated plaque formation and memory impairment. However, in some models, the correlation between memory loss and plaque formation is poor. Our lab has recently found a strong correlation between formaldehyde levels and cognitive impairment in AD patients and animal models. In the present study, we found that working memory was inversely correlated with formaldehyde levels in AβPP^Lon/Swe transgenic mice, which showed memory deficiency at 3 months of age but normal memory at 6 months. Impaired memory in 3-month-old mice was accompanied by higher levels of formaldehyde and hyperphosphorylated tau than controls. Administration of resveratrol, which is a formaldehyde scavenger, rescued the cognitive deficits in these mice by reducing formaldehyde levels and attenuating tau hyperphosphorylation. With increased expression of formaldehyde catalytic enzymes such as aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase III (ADH3), 6-month-old AβPP^Lon/Swe mice displayed similar levels of formaldehyde and working memory as controls. We discovered that brain formaldehyde levels were significantly associated with the progression of memory deficit in AβPP^Lon/Swe transgenic mice, and that recovery of memory was associated with formaldehyde reduction. Our findings provide valuable insights into the underlying mechanisms of AD.