Progressive neuropathology and cognitive decline in a single Arctic APP transgenic mouse model.
Neurobiol Aging
; 32(2): 280-92, 2011 Feb.
Article
en En
| MEDLINE
| ID: mdl-19329229
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 Aß 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Trastornos del Conocimiento
/
Alanina
/
Enfermedad de Alzheimer
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Glicina
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Neurobiol Aging
Año:
2011
Tipo del documento:
Article
País de afiliación:
Suecia
Pais de publicación:
Estados Unidos