Abstract

The inflammatory response is a fundamental driving force in the pathogenesis of Alzheimer’s disease (AD). In the setting of accumulating immunogenic Aß peptide assemblies, microglia, the innate immune cells of the brain, generate a non-resolving immune response and fail to adequately clear accumulating Aß peptides, accelerating neuronal and synaptic injury. Pathological, biomarker, and imaging studies point to a prominent role of the innate immune response in AD development, and the molecular components of this response are beginning to be unraveled. The inflammatory cyclooxygenase-PGE2 pathway is implicated in pre-clinical development of AD, both in epidemiology of normal aging populations and in transgenic mouse models of Familial AD. The cyclooxygenase-PGE₂ pathway modulates the inflammatory response to accumulating Aß peptides through actions of specific E-prostanoid G-protein coupled receptors.

Keywords: Alzheimer’s disease, microglia, amyloid beta, inflammation, cyclooxgenases, prostaglandin E₂, EP2 receptor, EP3 receptor, EP4 receptor.