Studies have demonstrated that the lack of ALDH2 activity caused by expression of the ALDH2*2 gene leads to accumulation of 4-HNE in the brains of transgenic mice and the death of neuronal cells, resulting in age-related neurodegeneration; this shows that ALDH2 can reduce 4-HNE–induced Aβ production and tau phosphorylation to prevent NFTs and SPs formation so as to inhibit neurotoxicity in AD [74]. Here, ALDH2 is linked to Alzheimer disease.