Intraneuronal Aβ accumulation precedes plaque formation in β-amyloid precursor protein and presenilin-1 double-transgenic mice

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Abstract

β-Amyloid peptides are key molecules that are involved in the pathology of Alzheimer's disease (AD). The source and place of the neurotoxic action of Aβ, however, is still a matter of controversial debates. In the present report, we studied the neuropathological events in a transgenic mouse model expressing human mutant β-amyloid precursor protein and human mutant presenilin-1 in neurons. Western blot and immunohistochemical analysis revealed that intracellular Aβ staining preceded plaque deposition, which started in the hippocampal formation. At later stages, many neuritic Aβ positive plaques were found in all cortical, hippocampal and many other brain areas. Interestingly, intraneuronal Aβ staining was no longer detected in the brain of aged double-transgenic mice, which correlates with the typical neuropathology in the brain of chronic AD patients.

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Acknowledgements

We would like to thank Professor Fred van Leuven (KU Leuven, Belgium) for the generous gift of the PDGFβ promoter construct. With kind support from the Fritz Thyssen Foundation and the Alzheimer Forschung Initiative e.V. (to T.A.B.) and the Deutsche Forschungsgemeinschaft (Mu901 to G.M. and T.A.B.). The expert technical assistance of Sophie Ligout, Gwenaell Ret, Brigitte Schombert, Nathalie Touchet, Ulrich Klatt, Sarah Pierschalski, Esther Barth, Nicole Feldmann and Andreas Porebski is

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Present address: NAP AG, Landsbergerstrasse 50, 80339 München, Germany

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