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 Alzheimer's disease (AD) brains. Although activated microglia seem to play a central role in the pathogenesis of AD, mechanisms of microglial activation by beta-amyloid as well as the nature of interaction between amyloid and microglia remain poorly understood. We previously reported a close morphological association between activated microglia and congophilic amyloid plaques in the brains of APP23 transgenic mice at both the light and electron microscopic levels [25]. In the present study, we have further examined the structural relationship between microglia and amyloid deposits by using postembedding immunogold labeling, serial ultrathin sectioning, and 3-dimensional reconstruction. Although bundles of immunogold-labeled amyloid fibrils were completely engulfed by microglial cytoplasm on single sections, serial ultrathin sectioning and three-dimensional reconstruction revealed that these amyloid fibrils are connected to extracellular amyloid deposits. These data demonstrate that extracellular amyloid fibrils form a myriad of finger-like channels with the widely branched microglial cytoplasm. We conclude that in APP23 mice a role of microglia in amyloid phagocytosis and intracellular production of amyloid is unlikely.
Stalder
M
M
Department of Neuropathology, Institute of Pathology, University of Basel, Basel, Switzerland.
Deller
T
T
Staufenbiel
M
M
Jucker
M
M
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D005110:Extracellular Space / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics*; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D014463:Ultrasonography
D016564:Amyloid beta-Protein Precursor