Expression of CAP37, a novel inflammatory mediator, in Alzheimerʹs disease

Recent evidence suggests that inflammation in the central nervous system plays an important role in the pathogenesis of Alzheimerʹs disease. However, the identity of the inflammatory mediators, cytokines, and reactive oxygen species, that orchestrate cell death and plaque biogenesis in Alzheimerʹs disease, have yet to be elucidated. We have identified a novel inflammatory mediator, CAP37 (Cationic Antimicrobial Protein Mr 37 kDa), that promotes mononuclear cell chemotaxis, adhesion of monocytes to endothelium, and release of oxygen radicals from monocytes. In the present immunocytochemical study, we demonstrate the expression of CAP37 in the cerebral microvasculature in Alzheimerʹs disease. CAP37 was not detected in brain vessels of normal controls or patients with other neuropathologic conditions such as Pickʹs, Parkinsonʹs, Binswangerʹs disease, Progressive Supranuclear Palsy, and Candida infection. Treatment of cerebral endothelial cultures with inflammatory mediators, cytokines or β-amyloid results in the induction of CAP37 expression. These in vitro data showing endothelial-CAP37 expression after β-amyloid treatment together with the previous demonstration that CAP37 stimulates mononuclear cell migration and activation, suggest that CAP37 could contribute to neuronal injury in Alzheimerʹs disease.