Possible involvement of transthyretin in hippocampal beta-amyloid burden and learning behaviors in a mouse model of Alzheimer's disease (TgCRND8).
Neurodegener Dis
; 7(1-3): 88-95, 2010.
Article
em En
| MEDLINE
| ID: mdl-20173334
ABSTRACT
BACKGROUND:
Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss, possibly triggered by the accumulation of beta-amyloid (Abeta) peptides and the hyperphosphorylation of Tau neurofilament protein. Recent findings have shown that transthyretin (TTR) is a potent scavenger of Abeta peptide deposits, suggesting a possible neuroprotective role for TTR in neurodegenerative processes associated with amyloidogenesis, such as AD.METHODS:
To investigate the relationship between TTR and Abeta deposition, we crossed mouse carrying a deletion of TTR (TTR(- or -)) with a transgenic mouse model of AD (TgCRND8), and Abeta burden and spatial learning capacities were evaluated at 4 and 6 months of age (exclusion of the 6 month-old TgCRND8/TTR(- or -) group due to low survival rate).RESULTS:
Rather surprisingly, Abeta plaque burden was significantly reduced in the hippocampus of 4-month-old TgCRND8/TTR(+ or -), and to a lesser extent in TgCRND8/TTR(- or -), as compared to age-matched TgCRND8/TTR(+ or +). No difference in plaque burden was found between any groups in 6-month-old animals. At 4 and 6 months of age, all populations of these hybrid transgenic mice displayed similar magnitude of spatial memory deficits in the Morris water maze task.CONCLUSION:
Since TgCRND8 mice represent an aggressive model of Abeta deposition with plaques developing as early as 3 months of age, along with spatial learning deficits, it may be already too late at 4 and 6 months of age to observe significant changes due to the deletion of the TTR gene.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pré-Albumina
/
Peptídeos beta-Amiloides
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Doença de Alzheimer
/
Hipocampo
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Deficiências da Aprendizagem
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article