Progressive neuronal injury associated with amyloid plaque formation in Alzheimer disease

J Neuropathol Exp Neurol. 1998 Jul;57(7):714-7. doi: 10.1097/00005072-199807000-00008.


Neuronal injury associated with amyloid plaque progression in Alzheimer disease was examined using TUNEL combined with beta-amyloid immunolabeling. There was a progressive increase in the frequency of TUNEL-positive neurons associated with plaque types representing a hypothesized sequence of plaque evolution, from 20% of neurons not associated with plaques to 40%, 70-80%, and 100% of neurons in diffuse, neuritic, and dense-core non-neuritic plaques, respectively. The total number of neurons associated with end-stage, dense-core, non-neuritic plaques declined by 70% (per unit plaque area) compared with neuritic plaque forms. This decline, together with the fact that virtually all of those remaining were TUNEL-positive, suggests that neuronal cell damage increases as plaques evolve from diffuse to more complex forms and that eventually all plaque-associated neurons are lost. This novel demonstration of neurotoxicity associated with amyloid plaque formation and progression suggests that plaque-associated neuronal injury is a major cause of neuronal loss in Alzheimer disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / analysis*
  • Apoptosis
  • Brain / pathology*
  • Female
  • Humans
  • Male
  • Neurons / pathology*
  • Plaque, Amyloid / pathology*


  • Amyloid beta-Peptides