Acetylcholinesterase-positive fiber deafferentation and cell shrinkage in the septohippocampal pathway of aged amyloid precursor protein london mutant transgenic mice

Francisca C. Bronfman, Dieder Moechars, Fred Van Leuven

Research output: Contribution to journalArticlepeer-review

79 Citations (Scopus)

Abstract

Several lines of evidence implicate a cholinergic deficit in Alzheimer's disease (AD). Transgenic mice that overexpress clinical mutants of the human amyloid precursor protein (APP) have been generated that recapitulate many aspects of AD. We now analyzed the cholinergic system in aged APP/London transgenic mice. The major finding was the reorganization of acetylcholinesterase-positive fibers within the hippocampus and the reduced size of cholinergic cells in the medial septum. The reduction of acetylcholinesterase-positive fibers in the subiculum together with increased fiber density in the CA1 and in the dentate gyrus suggests a synaptic sprouting compensatory mechanism within the hippocampus. In the cortex, amyloid plaques were associated with intense acetylcholinesterase activity and surrounded by dystrophic acetylcholinesterase-positive fibers. Nevertheless, the overall pattern of cholinergic innervation was unchanged. These results demonstrate that overexpression of APP/London caused, besides amyloid plaques in aged mouse brain, also cholinergic deafferentation and cholinergic cell shrinkage. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)152-168
Number of pages17
JournalNeurobiology of Disease
Volume7
Issue number3
DOIs
Publication statusPublished - Jun 2000
Externally publishedYes

Keywords

  • Aging
  • Alzheimer's disease
  • Amyloid plaques
  • Cholinergic system
  • Transgenic mice models

ASJC Scopus subject areas

  • Neurology

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