Progressive neuropathology and cognitive decline in a single Arctic APP transgenic mouse model
| Autor: | Shunwei Zhu, Annica Rönnbäck, Caroline Graff, Bengt Winblad, Mikio Aoki, Lena Lilius, Jan Näslund, Karin Dillner |
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| Rok vydání: | 2011 |
| Předmět: |
Genetically modified mouse
Aging Amyloid beta Glycine Enzyme-Linked Immunosorbent Assay Mice Transgenic Neuropathology Statistics Nonparametric Amyloid beta-Protein Precursor Mice Alzheimer Disease Escape Reaction medicine Animals Humans Dementia Cognitive decline Maze Learning Alanine Amyloid beta-Peptides biology Learning Disabilities General Neuroscience Age Factors Brain medicine.disease Peptide Fragments Barnes maze Mutation Mutation (genetic algorithm) Disease Progression Exploratory Behavior biology.protein Neurology (clinical) Geriatrics and Gerontology Alzheimer's disease Cognition Disorders Psychology Neuroscience Developmental Biology |
| Zdroj: | Neurobiology of Aging. 32:280-292 |
| ISSN: | 0197-4580 |
| Popis: | The Arctic APP mutation (E693G) leads to dementia with clinical features similar to Alzheimer disease (AD), but little is known about the pathogenic mechanism of this mutation. To address this question, we have generated a transgenic mouse model, TgAPParc, with neuron-specific expression of human APP with the Arctic mutation (hAPParc). Heterozygous mice from two separate founder lines with different levels of expression of hAPParc were analyzed with respect to brain morphology and behavior every 3 months until the age of 18 months. Standard histological stainings and immunohistochemistry using a panel of Aβ antibodies showed an age- and dose-dependant progression of amyloid deposition in the brain, starting in the subiculum and spreading to the thalamus. Cognitive behavioral testing revealed deficits in hippocampus-dependent spatial learning and memory in the Barnes maze test. This study demonstrates that the Arctic APP mutation is sufficient to cause amyloid deposition and cognitive dysfunction, and thus the TgAPParc mouse model provides a valuable tool to study the effect of the Arctic mutation in vivo without possible confounding effect of other APP mutations. |
| Databáze: | OpenAIRE |
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