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| Bart P.F. Rutten |
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Universiteitssingel 50, PO BOX 616, University of Maastricht, The Netherlands
e-mail: B.Rutten@NP.unimaas.nl |
Poster Presentation: |
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| PLAQUE INDUCED NEURONAL LOSS IN THE HIPPOCAMPUS OF MICE DOUBLY TRANSGENIC FOR MUTANT HUMAN AMYLOID PRECURSOR PROTEIN AND PRESENILIN-1. |
| B.P.F. Rutten 1,2,6; A. Pielen2; O. Wirths3,6; S. Schäfer1,3,6; H. Korr2,6; H.W.M. Steinbusch1,6; L. Pradier4; T.A. Bayer3,6; C. Schmitz1,5,6. | |
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1. Dept. Psychiatry and Neuropsychology, University of Maastricht, Maastricht, Netherlands 2. Dept. Anatomy and Cell Biology, RWTH University Aachen, Aach |
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| Among the classical pathological hallmarks of Alzheimer’s disease (AD), the role of ß-amyloid containing plaques has received most attention during the last years. Many novel approaches to prevent or treat AD focus upon preventing the formation of ß-amyloid or degradating ß-amyloid containing plaques. Despite this central role in AD research, the actual neurotoxic effect of ß- amyloid containing plaques on neurons has not been shown in vivo so far. Here we studied mice singly transgenic for human mutant presenilin-1 (PS-1 M146L) and mice doubly transgenic for human mutant amyloid precursor protein (APP)751 (KM670/671NL and V717I) and human mutant PS-1. The latter mice show abundant expression of APP in pyramidal neurons of the hippocampus and cortex and in dentate gyrus granule cells. Furthermore, ß-amyloid containing plaques are formed in hippocampus, cortex and striatum in the brains of the APP/PS1 transgenic mice. The aim of this study was to investigate the effects of mutant human APP and PS1 on the neuronal numbers and volumes of the hippocampal pyramidal and granule layer in these transgenic mice. Neuronal loss was evaluated by investigating the volumes of the hippocampal granule and pyramidal cell layers, and the numbers of the hippocampal granule and pyramidal cells of 17-month-old APP/PS-1 mice with design-based stereological methods. Main resuls: while hemizygous PS-1 transgenic mice did not show any sign for neuronal loss, APP/PS-1 transgenic mice elicited a 25% reduction in the number of hippocampal pyramidal cells. By applying additional stereological techniques, we could show that this loss of neurons was mainly associated with plaques. These observations indicate that - besides the formation of neurofibrillary tangles - plaque formation is a crucial mechanism in AD-related neuronal loss.
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