β-amyloid stimulates murine postnatal and adult microglia cultures in a unique manner

Reactive microglia are commonly observed in association with the beta-amyloid (A beta) plaques of Alzheimer's disease brains. This localization supports the hypothesis that A beta is a specific activating stimulus for microglia. A variety of in vitro studies have used postnatal derived rodent microglia cultures to characterize the ability of A beta to stimulate these cells. However, it is unclear whether this paradigm accurately models conditions in aged animals. To determine whether A beta stimulatory phenotypes differ between young and adult microglia, we established cultures of acutely isolated adult murine cortical microglia to compare with postnatal derived microglial cultures. Although cells from both ages expressed robust immunoreactivity for CD68 and CD11b, their responses to activating stimuli differed. Fibrillar A beta was rapidly phagocytosed by postnatal microglia and both oligomeric and fibrillar peptide stimulated increased tumor necrosis factor alpha(TNF alpha) secretion. However, A beta oligomers but not fibrils stimulated TNF alpha secretion from adult microglia. More importantly, adult microglia had diminished ability to phagocytose A beta fibrils. These findings demonstrate that adult microglia respond to A beta fibril stimulation uniquely from postnatal cells and suggest that adult rather than postnatal microglia cultures are more appropriate for modeling proinflammatory changes in the aged CNS.