Acetylcholinesterase-Positive Fiber Deafferentation and Cell Shrinkage in the Septohippocampal Pathway of Aged Amyloid Precursor Protein London Mutant Transgenic Mice

Bronfman, Francisca C.; Moechars, Dieder; van Leuven, Fred


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.

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Título de la Revista: Neurobiology of Disease
Volumen: 7
Número: 3
Fecha de publicación: 2000
Página de inicio: 152
Página final: 168