Intraneuronal Abeta accumulation and origin of plaques in Alzheimer's disease

Neurobiol Aging. 2005 Oct;26(9):1235-44. doi: 10.1016/j.neurobiolaging.2005.05.022.


Plaques are a defining neuropathological hallmark of Alzheimer's disease (AD) and the major constituent of plaques, the beta-amyloid peptide (Abeta), is considered to play an important role in the pathophysiology of AD. But the biological origin of Abeta plaques and the mechanism whereby Abeta is involved in pathogenesis have been unknown. Abeta plaques were thought to form from the gradual accumulation and aggregation of secreted Abeta in the extracellular space. More recently, the accumulation of Abeta has been demonstrated to occur within neurons with AD pathogenesis. Moreover, intraneuronal Abeta accumulation has been reported to be critical in the synaptic dysfunction, cognitive dysfunction and the formation of plaques in AD. Here we provide a historical overview on the origin of plaques and a discussion on potential biological and therapeutic implications of intraneuronal Abeta accumulation for AD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Humans
  • Models, Biological
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Neurons / metabolism*
  • Neurons / pathology
  • Neurons / ultrastructure
  • Plaque, Amyloid / metabolism*


  • Amyloid beta-Peptides