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

Neurobiol Aging. May-Jun 2001;22(3):427-34. doi: 10.1016/s0197-4580(01)00209-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Cytoplasm / metabolism
  • Cytoplasm / ultrastructure
  • Extracellular Space / diagnostic imaging
  • Extracellular Space / metabolism
  • Humans
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism*
  • Microglia / pathology
  • Microglia / ultrastructure
  • Microscopy, Electron
  • Mutation / genetics*
  • Plaque, Amyloid / metabolism*
  • Plaque, Amyloid / pathology
  • Plaque, Amyloid / ultrastructure
  • Ultrasonography

Substances

  • Amyloid beta-Protein Precursor