ENDOGENOUS APOLIPOPROTEIN-E SUPPRESSES LPS-STIMULATED MICROGLIAL NITRIC-OXIDE PRODUCTION

THE human apolipoprotein (ape) E4 isoform is associated with an increa sed risk for Alzheimer's disease (AD) and poor prognosis after acute C NS injury. Addition of human apoE inhibits murine microglial activatio n in culture, suggesting that microglia might be an important physiolo gical target of apoE. In the present study, we examined the role of en dogenous murine apoE in modulating microglial nitric oxide (NO) produc tion following lipopolysaccharide (LPS) stimulation. Brain cultures fr om apoE-deficient mouse pups showed enhanced NO production relative to cultures from wildtype mice and from transgenic mice expressing the h uman apoE3 isoform, demonstrating that endogenous apoE produced by gli al cultures is capable of inhibiting microglial function. ApoE produce d within the brain may suppress microglial reactivity and thus alter t he CNS response to acute and chronic injury.