Ablation of cellular prion protein does not ameliorate abnormal neural network activity or cognitive dysfunction in the J20 line of human amyloid precursor protein transgenic mice.
J Neurosci
; 31(29): 10427-31, 2011 Jul 20.
Article
em En
| MEDLINE
| ID: mdl-21775587
ABSTRACT
Previous studies suggested that the cellular prion protein (PrP(c)) plays a critical role in the pathogenesis of Alzheimer's disease (AD). Specifically, amyloid-ß (Aß) oligomers were proposed to cause synaptic and cognitive dysfunction by binding to PrP(c). To test this hypothesis, we crossed human amyloid precursor protein (hAPP) transgenic mice from line J20 onto a PrP(c)-deficient background. Ablation of PrP(c) did not prevent the premature mortality and abnormal neural network activity typically seen in hAPPJ20 mice. Furthermore, hAPPJ20 mice with or without PrP(c) expression showed comparably robust abnormalities in learning and memory and in other behavioral domains at 6-8 months of age. Notably, these abnormalities are not refractory to therapeutic manipulations in general they can be effectively prevented by interventions that prevent Aß-dependent neuronal dysfunction also in other lines of hAPP transgenic mice. Thus, at least in this model, PrP(c) is not an important mediator of Aß-induced neurological impairments.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Precursor de Proteína beta-Amiloide
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Transtornos Cognitivos
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Proteínas PrPSc
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article