In addition to COX-2 enzymes role in inflammation, the formation of amyloid plaques and neurofibrillary tangles in the brain, the review emphasizes that COXs-2 have a crucial role in normal synaptic activity and plasticity, and have a relationship with acetylcholine, tau protein, and beta-amyloid (Aβ) which are the main causes of Alzheimer's disease. This evidence concerns the gene PTGS2 and Alzheimer disease.