Secretory PLA(2)-IIA: a new inflammatory factor for Alzheimer's disease

Secretory phospholipase A(2)-IIA (sPLA(2)-IIA) is an inflammatory protein known to play a role in the pathogenesis of many inflammatory diseases. Although this enzyme has also been implicated in the pathogenesis of neurodegenerative diseases, there has not been a direct demonstration of its expression in diseased human brain. In this study, we show that sPLA(2)-IIA mRNA is up-regulated in Alzheimer's disease (AD) brains as compared to non-demented elderly brains (ND). We also report a higher percentage of sPLA(2)-IIA-immunoreactive astrocytes present in AD hippocampus and inferior temporal gyrus (ITG). In ITG, the majority of sPLA(2)-IIA-positive astrocytes were associated with amyloid β (Aβ)-containing plaques. Studies with human astrocytes in culture demonstrated the ability of oligomeric Aβ(1–42 )and interleukin-1β (IL-1β) to induce sPLA(2)-IIA mRNA expression, indicating that this gene is among those induced by inflammatory cytokines. Since exogenous sPLA(2)-IIA has been shown to cause neuronal injury, understanding the mechanism(s) and physiological consequences of sPLA(2)-IIA upregulation in AD brain may facilitate the development of novel therapeutic strategies to inhibit the inflammatory responses and to retard the progression of the disease.