Diffuse amyloid deposition, but not plaque number, is reduced in amyloid precursor protein/presenilin 1 double-transgenic mice by pathway lesions

Academic Article


  • Alzheimer's disease (AD) is the most common form of dementia in the elderly, and the characteristic pathological hallmarks of the disease are neuritic plaques and neurofibrillary tangles. The sequence of events leading to the extracellular deposition of amyloidβ (Aβ) peptides in plaques or in diffuse deposits is not clear. Here we investigate the relation between disrupted axonal transport of amyloid precursor protein (APP) and/or Aβ and the deposition of Aβ in the deafferented terminal fields in APP/presenilin 1 double-transgenic AD-model mice. In the first experiment we ablated entorhinal cortex neurons and examined the subsequent changes in amyloid deposition in the hippocampus 1 month later. We show that there is a substantial reduction in the amount of diffuse amyloid deposits in the denervated areas of the hippocampus. Further, to investigate the effects of long-term deafferentation, in a second experiment we cut the fimbria-fornix and analyzed the brains 11 months post-lesion. Diffuse amyloid deposits in the deafferented terminal fields of area CA1 and subiculum were dramatically reduced as assessed by image analysis of the Aβ load. Our findings indicate that neuronal ablations decrease diffuse amyloid deposits in the terminal fields of these neurons, and, further, that pathway lesions similarly decrease the amount of diffuse amyloid deposits in the terminal fields of the lesioned axons. Together, this suggests that the axonal transport of APP and/or Aβ and subsequent secretion of Aβ at terminals plays an important role in the deposition of Aβ protein in Alzheimer's disease, and, further, that diffuse deposits do not develop into plaques. © 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.
  • Authors

    Published In

  • Neuroscience  Journal
  • Digital Object Identifier (doi)

    Author List

  • Van Groen T; Liu L; Ikonen S; Kadish I
  • Start Page

  • 1185
  • End Page

  • 1197
  • Volume

  • 119
  • Issue

  • 4