Abstract
beta-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 Abeta, 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 beta-amyloid precursor protein and human mutant presenilin-1 in neurons. Western blot and immunohistochemical analysis revealed that intracellular Abeta staining preceded plaque deposition, which started in the hippocampal formation. At later stages, many neuritic Abeta positive plaques were found in all cortical, hippocampal and many other brain areas. Interestingly, intraneuronal Abeta 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.
MeSH terms
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Alzheimer Disease / genetics
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Alzheimer Disease / metabolism*
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Alzheimer Disease / physiopathology
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Amyloid beta-Peptides / genetics
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Amyloid beta-Peptides / metabolism*
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Amyloid beta-Protein Precursor / genetics
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Amyloid beta-Protein Precursor / metabolism*
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Animals
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Brain / metabolism*
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Brain / pathology
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Brain / physiopathology
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Cerebral Cortex / metabolism
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Cerebral Cortex / pathology
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Cerebral Cortex / physiopathology
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Gliosis / genetics
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Gliosis / pathology
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Gliosis / physiopathology
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Hippocampus / metabolism
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Hippocampus / pathology
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Hippocampus / physiopathology
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Humans
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Immunohistochemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mice, Transgenic / genetics
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Mice, Transgenic / metabolism
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Mutation / genetics
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Neurons / metabolism*
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Neurons / pathology
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Plaque, Amyloid / genetics
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Plaque, Amyloid / metabolism*
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Plaque, Amyloid / pathology
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Presenilin-1
Substances
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Amyloid beta-Peptides
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Amyloid beta-Protein Precursor
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Membrane Proteins
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PSEN1 protein, human
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Presenilin-1