Dystrophic neurite formation associated with age-related β amyloid deposition in the neocortex: Clues to the genesis of neurofibrillary pathology

James C. Vickers, Devika Chin, Ann Marie Edwards, Viola Sampson, Clive Harper, John Morrison

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71 Scopus citations


The formation of dystrophic neurites associated with β amyloid plaques in Alzheimer's disease (AD) appears to involve a transformation of normal neuronal cytoskeletal proteins. In order to investigate what may be the earliest neuronal changes associated with the development of dystrophic neurites, we have examined the neurochemical profile of abnormal neuritic processes associated with the β amyloid deposition in non-AD, aged cases. In all non-AD individuals demonstrating some degree of β amyloid deposition in the superior frontal gyrus, clustered swollen and ring-like structures, located principally in layers II and III, were labeled with antibodies to phosphorylated and nonphosphorylated domains of the middle and high molecular weight neurofilament subunits. These abnormal neurites were not immunolabeled for tau or ubiquitin or stained with thioflavine S. Double labeling for neurofilaments and thioflavine S confirmed that these clusters of dystrophic neurites were associated with plaque-like deposits. These results show that anatomically and neurochemically specific forms of dystrophic neurites can occur in non-AD cases that contain β amyloid deposition. If these abnormal neurites correspond to an immature form of the dystrophic neurites found in the neuritic plaques of Alzheimer's disease, then neurofibrillary pathology associated with this disease may begin with an initial misprocessing and accumulation of neurofilament proteins. Furthermore, these data are consistent with the proposal that the development of neurofibrillary pathology may begin with neurofilamentous hypertrophy in damaged distal processes followed by reactive changes in the cell bodies of origin of these fibers involving cytoskeletal alterations that ultimately lead to neurofibrillary tangle formation.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalExperimental Neurology
Issue number1
StatePublished - Jan 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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