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Journal of Neural Transmission

, Volume 113, Issue 9, pp 1225–1241 | Cite as

Regional acetylcholinesterase activity and its correlation with behavioral performances in 15-month old transgenic mice expressing the human C99 fragment of APP

  • M. Dumont
  • R. Lalonde
  • J.-F. Ghersi-Egea
  • K. Fukuchi
  • C. Strazielle
Article

Summary.

In addition to Aβ plaques and neurofibrillary tangles, Alzheimer’s disease (AD) is characterized by increased brain levels of APP C-terminal fragments. In the present investigation, the cholinergic innervation in forebrain regions of transgenic mice (Tg13592) expressing the human βAPP C99 fragment was compared to that of non-transgenic controls by measuring the activity of the non-specific catabolic enzyme, acetylcholinesterase (AChE). The AchE activity of Tg13592 mice was altered in several regions implicated in the functional loop of regulation between septum and hippocampus, vulnerable in Alzheimer pathology and critically involved in cognitive functions. In particular, AChE activity was upregulated in three basal forebrain regions containing cholinergic cell bodies, prelimbic cortex, anterior subiculum, and paraventricular thalamus, but downregulated in lateral septum and reticular thalamus. The increased activity in medial septum and anterior subiculum was linearly correlated with poor performances in a spatial learning task, possibly due to cell stress mechanisms. Because of some similarities in terms of neurochemistry and behavior, this mouse model may be of use for studying prodromal AD.

Keywords: Alzheimer’s disease, acetylcholinesterase, cholinergic neuron, transgenic mice, APP C99 fragment. 

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • M. Dumont
    • 1
  • R. Lalonde
    • 1
  • J.-F. Ghersi-Egea
    • 2
  • K. Fukuchi
    • 3
  • C. Strazielle
    • 4
  1. 1.Université de Rouen, Faculté de Médecine et de Pharmacie, INSERM U614RouenFrance
  2. 2.Université de Lyon-Laennec, INSERM U433, Faculté de MédecineLyonFrance
  3. 3.Department of Biomedical and Therapeutic SciencesUniversity of Illinois College of MedicinePeoriaUSA
  4. 4.Université Henri Poincaré, Nancy I, Laboratoire de Pathologie Moléculaire et Cellulaire des Nutriments, INSERM U724, and Service de Microscopie Electronique, Faculté de MédecineVandoeuvre-les-NancyFrance

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