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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 an...

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Published in:Neurobiology of aging 2001-05, Vol.22 (3), p.427-434
Main Authors: STALDER, M, DELLER, T, STAUFENBIEL, M, JUCKER, M
Format: Article
Language:English
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Summary: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.
ISSN:0197-4580
1558-1497
DOI:10.1016/S0197-4580(01)00209-3