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Hippocampal neuron loss is greater than amyloid plaque load in a transgenic mouse model of Alzheimer’s disease

Schmitz, Christoph; Rutten, Bart P.F.; Pielen, Andrea; Schafer, Stephanie; Wirths, Oliver; Tremp, Gunter; Czech, Christian; Blanchard, Veronique; Multhaup, Gerd; Rezaie, Payam; Korr, Hubert; Steinbusch, Harry W.M.; Pradier, Laurent and Bayer, Thomas A. (2004). Hippocampal neuron loss is greater than amyloid plaque load in a transgenic mouse model of Alzheimer’s disease. American Journal of Pathology, 164(4) pp. 1495–1502.

URL: http://ajp.amjpathol.org/article/S0002-9440(10)632...
DOI (Digital Object Identifier) Link: http://dx.doi.org/10.1016/S0002-9440(10)63235-X
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Abstract

According to the "amyloid hypothesis of Alzheimer's disease," beta-amyloid is the primary driving force in Alzheimer's disease pathogenesis. Despite the development of many transgenic mouse lines developing abundant beta-amyloid-containing plaques in the brain, the actual link between amyloid plaques and neuron loss has not been clearly established, as reports on neuron loss in these models have remained controversial. We investigated transgenic mice expressing human mutant amyloid precursor protein APP751 (KM670/671NL and V717I) and human mutant presenilin-1 (PS-1 M146L). Stereologic and image analyses revealed substantial age-related neuron loss in the hippocampal pyramidal cell layer of APP/PS-1 double-transgenic mice. The loss of neurons was observed at sites of Abeta aggregation and surrounding astrocytes but, most importantly, was also clearly observed in areas of the parenchyma distant from plaques. These findings point to the potential involvement of more than one mechanism in hippocampal neuron loss in this APP/PS-1 double-transgenic mouse model of Alzheimer's disease.

Item Type: Journal Article
Copyright Holders: 2004 American Society for Investigative Pathology
ISSN: 1525-2191
Academic Unit/Department: Science > Life, Health and Chemical Sciences
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 2353
Depositing User: Payam Rezaie
Date Deposited: 12 Jun 2006
Last Modified: 27 Mar 2014 10:30
URI: http://oro.open.ac.uk/id/eprint/2353
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