Integrated communications between cyclooxygenase‐2 and Alzheimer's disease

ABSTRACT Elevated levels of cyclooxygenase‐2 (COX‐2) and prostaglandins (PGs) are involved in the pathogenesis of Alzheimer's disease (AD), which is characterized by the accumulation of β‐amyloid protein (Aβ) and tau hyperphosphorylation. However, the gaps in our knowledge of the roles of COX‐2 and PGs in AD have not been filled. Here, we summarized the literature showing that COX‐2 dysregulation obviously influences abnormal cleavage of β‐amyloid precursor protein, aggregation and deposition of Aβ in β‐amyloid plaques and the inclusion of phosphorylated tau in neurofibrillary tangles. Neuroinflammation, oxidative stress, synaptic plasticity, neurotoxicity, autophagy, and apoptosis have been assessed to elucidate the mechanisms of COX‐2 regulation of AD. Notably, an imbalance of these factors ultimately produces cognitive decline. The current review substantiates our understanding of the mechanisms of COX‐2–induced AD and establishes foundations for the design of feasible therapeutic strategies to treat AD.—Guan, P.‐P., Wang, P. Integrated communications between cyclooxygenase‐2 and Alzheimer's disease. FASEB J. 33, 13–33 (2019). www.fasebj.org