Enoxaparin treatment administered at both early and late stages of amyloid ß deposition improves cognition of APPswe/PS1dE9 mice with differential effects on brain Aß levels.
Neurobiol Dis
; 40(1): 340-7, 2010 Oct.
Article
em En
| MEDLINE
| ID: mdl-20600909
ABSTRACT
Enoxaparin (Enox), a low molecular weight heparin, has been shown to lower brain amyloid beta (A beta) load in a mouse model for Alzheimer's disease. However, the effect of Enox on cognition was not studied. Therefore, we examined the effect of peripheral Enox treatment on cognition and brain A beta levels in the APPswe/PS1dE9 mouse model by giving injections at an early (starting at 5 months of age) and late (starting at 10 and 12 months of age) stage of A beta accumulation for 3 months. Although Enox had no effect on behaviour in the open field at any age, it improved spatial memory in the Morris water maze in 5-, 10- and 12-month-old mice. Furthermore, Enox treatment seemed to decrease guanidine HCl-extracted brain A beta levels at 5 months of age, but significantly increased guanidine HCl-extracted A beta 42 and A beta 40 levels in both 10- and 12-month-old mice. In vitro, Enox increased aggregation of A beta, even when A beta was pre-aggregated. In conclusion, Enox treatment, either at an early or a late stage of A beta accumulation, could improve cognition in APPswe/PS1dE9 mice. However, since Enox treatment at an early stage of A beta accumulation decreased guanidine HCl-extracted A beta levels and Enox treatment at a late stage enhanced guanidine HCl-extracted A beta levels, it seems that Enox influences A beta deposition differently at different stages of A beta pathology. In any case, our study suggests that enoxaparin treatment has potential as a therapeutic agent for Alzheimer's disease.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
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Transtornos Cognitivos
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Enoxaparina
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Placa Amiloide
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Doença de Alzheimer
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article