Cytosolic phospholipase A(2) (cPLA(2)) immunoreactivity is elevated in Alzheimer's disease brain

Phospholipase A(2) (PLA(2)) is the key enzyme that initiates the arachidonic acid cascade, which leads to the generation of multiple eicosanoid products, Many of these products are believed to play an important role in the inflammatory process. Activation of FLAP is observed under pathological conditions where inflammation is present. Cytosolic PLA(2) (cPLA(2)) is activated by very low levels of calcium and is thought to control receptor-mediated eicosanoid production and to participate in intracellular signal transduction processes. In view of the presence of numerous inflammatory mediators and acute phase proteins in the Alzheimer's disease (AD) brain, localization of cPLA(2) in AD brain was evaluated and compared to that observed in nonneurologically diseased controls. In this study, a monoclonal antibody raised against cPLA(2) was used to immunostain tissue sections of human cerebral cortex. Five AD cases and six neurologically normal cases were evaluated in the occipital cortex and the cerebellum. Two of the AD cases were also examined in other cortical regions. Granular-like staining with anti-cPLA(2) was found to be associated with astrocytes in the cortex of both control and AD cases. Colocalization with GFAP confirmed that cPLA(2) immunoreactivity is associated almost exclusively with protoplasmic astrocytes. Staining was abolished when sections were labeled with antibody that had been preadsorbed with purified cPLA(2). In AD brain, cPLA(2) immunoreactive astrocytes were greater in number and more intensely stained than those in control cases. cPLA(2) immunoreactivity was virtually absent in the cerebellum of AD and control cases, despite the presence in this region of diffuse amyloid in two AD cases and amyloid angiopathy in a third case. In the cortex, cPLA(2) immunoreactive astrocytes were detected in regions that contained numerous AP deposits. The finding of elevated levels of cPLA(2) immunoreactivity in AD brain supports the hypothesis that there is an active inflammatory process occurring in AD. (C) 1996 Academic Press, Inc.