Neurotoxicity and memory deficits induced by soluble low-molecular-weight amyloid-ß1-42 oligomers are revealed in vivo by using a novel animal model.
J Neurosci
; 32(23): 7852-61, 2012 Jun 06.
Article
em En
| MEDLINE
| ID: mdl-22674261
ABSTRACT
Neuronal and synaptic degeneration are the best pathological correlates for memory decline in Alzheimer's disease (AD). Although the accumulation of soluble low-molecular-weight amyloid-ß (Aß) oligomers has been suggested to trigger neurodegeneration in AD, animal models overexpressing or infused with Aß lack neuronal loss at the onset of memory deficits. Using a novel in vivo approach, we found that repeated hippocampal injections of small soluble Aß(1-42) oligomers in awake, freely moving mice were able to induce marked neuronal loss, tau hyperphosphorylation, and deficits in hippocampus-dependent memory. The neurotoxicity of small Aß(1-42) species was observed in vivo as well as in vitro in association with increased caspase-3 activity and reduced levels of the NMDA receptor subunit NR2B. We found that the sequestering agent transthyretin is able to bind the toxic Aß(1-42) species and attenuated the loss of neurons and memory deficits. Our novel mouse model provides evidence that small, soluble Aß(1-42) oligomers are able to induce extensive neuronal loss in vivo and initiate a cascade of events that mimic the key neuropathological hallmarks of AD.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Peptídeos beta-Amiloides
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Síndromes Neurotóxicas
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Transtornos da Memória
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article