Minocycline affects microglia activation, Aβ deposition, and behavior in APP-tg mice

Activated microglia and reactive astrocytes invade and surround cerebral P amyloid (A beta) plaques in Alzheimer's disease (AD), but the role of microglia in plaque development is still unclear. In this study, minocycline was administered for 3 months, prior to and early in A beta plaque formation in amyloid precursor protein transgenic mice (APP-tg). When minocycline was given to younger mice, there was a small but significant increase in A beta deposition in the hippocampus, concurrent with improved cognitive performance relative to vehicle treated mice. If APP-tg mice received minocycline after A beta deposition had begun, microglial activation was suppressed but this did not affect A beta deposition or improve cognitive performance. In vitro studies demonstrated that minocycline suppressed microglial production of IL-1 beta., IL-6, TNF, and NGF. Thus, minocycline has different effects on A beta plaque deposition and microglia activation depending on the age of administration. Our data suggest that this may be due to the effects of minocycline on microglial function. Therefore, anti-inflammatory therapies to suppress microglial activation or function may reduce cytokine production but enhance A beta plaque formation early in AD. (c) 2006 Wiley-Liss, Inc.