β淀粉样蛋白(Aβ)沉积形成斑块是阿尔茨海默病(AD)的病理标志之一.以β淀粉样前体蛋白(AβPP)为基础的转基因小鼠模型表现出斑块形成加速和记忆损伤.然而,在一些模型中,记忆丧失与斑块形成的相关性较差.我们实验室最近报道了AD患者和动物模型的认知障碍与其体内甲醛水平有很强的相关性.本研究发现,AβPPLon/Swe转基因小鼠3月龄时表现出记忆缺陷,而在6月龄时记忆正常,其工作记忆与甲醛水平变化相反.与对照组相比,3月龄小鼠记忆受损伴随着甲醛水平的增高和过度磷酸化tau的增加.腹腔注射甲醛清除剂白藜芦醇可通过降低甲醛水平和tau蛋白的过度磷酸化,挽回小鼠的记忆损伤.6月龄AβPPLon/Swe小鼠甲醛水平和工作记忆与对照组相似,伴随甲醛降解酶ALDH2和ADH3表达增加.结果 显示,在AβPPLon/Swe转基因小鼠中,大脑甲醛水平与记忆变化进程显著相关,且记忆的恢复与甲醛水平下降相关.该研究为揭示阿尔茨海默病机制研究提供了新视角.“,”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 AβPPLon/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 AβPPLon/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 AβPPLon/Swe transgenic mice,and that recovery of memory was associated with formaldehyde reduction.Our findings provide valuable insights into the underlying mechanisms of AD.