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Re-evaluation of the structural organization of neuritic plaques in Alzheimer's disease

Academic Article
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Overview

authors

  • Masliah, E.
  • Mallory, M.
  • Deerinck, T.
  • DeTeresa, R.
  • Lamont, S.
  • Miller, A.
  • Terry, R. D.
  • Carragher, Bridget
  • Ellisman, M.

publication date

  • November 1993

journal

  • Journal of Neuropathology and Experimental Neurology  Journal

abstract

  • We re-examined the relationship among synaptic pathology, subcellular abnormalities within neurites in the plaques and beta-amyloid deposits of Alzheimer's disease (AD) using laser confocal imaging and computer-aided serial section reconstruction techniques. Analysis of serial optical sections of neuritic plaques double-immunolabeled for anti-beta-amyloid/anti-tau-2 revealed that 35% of this type of plaque contained a dense amyloid core with clusters of peripheral abnormal neurites. The other 65% were without a dense core and were mainly composed of abundant abnormal neuritic clusters with bundles of amyloid distributed throughout the neuritic plaque. While two-dimensional (2-D) analysis of the plaques has suggested that neurites are distributed in the plaque periphery with beta-amyloid localized in its center, serial section analysis showed the opposite arrangement can also be true. Three-dimensional (3-D) reconstructions of serial optical sections showed that the tau-positive tortuous axons clustered in the neuritic plaques were often continuous with synaptophysin-positive distended terminals. Analysis of electron micrographs from serial sections showed continuity among the different segments of the neurites. Further analysis of the computer generated 3-D reconstructed neuritic plaques (both from serial electron micrographs and serial optical sections), viewed as continuous rotating loops, confirmed that a great majority of the plaque volume was occupied by the clustered and continuous abnormal neurites, while the amyloid fibrils were compressed and displaced to the periphery of the plaque. The 3-D imaging of the neuritic plaques in AD suggests a more widespread and active neuritic damage than that predicted from 2-D observations.(ABSTRACT TRUNCATED AT 250 WORDS)

subject areas

  • Aged
  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Cerebral Cortex
  • Diagnosis, Computer-Assisted
  • Humans
  • Immunohistochemistry
  • Microscopy, Electron
  • Neurites
  • Synapses
  • Synaptophysin
  • tau Proteins
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Research

keywords

  • 3-DIMENSIONAL RECONSTRUCTION
  • ALZHEIMERS DISEASE
  • LASER CONFOCAL IMAGING
  • NEURITIC PLAQUE
  • SYNAPTOPHYSIN
  • TAU
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Identity

International Standard Serial Number (ISSN)

  • 0022-3069

Digital Object Identifier (DOI)

  • 10.1097/00005072-199311000-00009

PubMed ID

  • 8229081
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Additional Document Info

start page

  • 619

end page

  • 632

volume

  • 52

issue

  • 6

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