3D-reconstruction of microglia and amyloid in APP23 transgenic mice: no evidence of intracellular amyloid

Microglia cells are closely associated with compact amyloid plaques in Alzh eimer's disease (AD) brains. Although activated microglia seem to play a ce ntral role in the pathogenesis of AD, mechanisms of microglial activation b y beta -amyloid as well as the nature of interaction between amyloid and mi croglia remain poorly understood. We previously reported a close morphologi cal association between activated microglia and congophilic amyloid plaques in the brains of APP23 transgenic mice at both the light and electron micr oscopic levels [25]. In the present study, we have further examined the str uctural relationship between microglia and amyloid deposits by using postem bedding immunogold labeling, serial ultrathin sectioning, and 3-dimensional reconstruction. Although bundles of immunogold-labeled amyloid fibrils wer e completely engulfed by microglial cytoplasm on single sections, serial ul trathin sectioning and three-dimensional reconstruction revealed that these amyloid fibrils are connected to extracellular amyloid deposits. These dat a demonstrate that extracellular amyloid fibrils form a myriad of finger-li ke channels with the widely branched microglial cytoplasm. We conclude that in APP23 mice a role of microglia in amyloid phagocytosis and intracellula r production of amyloid is unlikely. (C) 2001 Elsevier Science Inc. All rig hts reserved.