Enoxaparin treatment administered at both early and late stages of amyloid beta deposition improves cognition of APPswe/PS1dE9 mice with differential effects on brain A beta levels.
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Publication year
2010Source
Neurobiology of Disease, 40, 1, (2010), pp. 340-7ISSN
Annotation
01 oktober 2010
Publication type
Article / Letter to editor
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Organization
Neurology
Laboratory of Genetic, Endocrine and Metabolic Diseases
Cell Biology (UMC)
Anatomy
Cognitive Neuroscience
Pathology
Journal title
Neurobiology of Disease
Volume
vol. 40
Issue
iss. 1
Page start
p. 340
Page end
p. 7
Subject
DCN 2: Functional Neurogenomics; DCN 3: Neuroinformatics; NCMLS 4: Energy and redox metabolism; ONCOL 3: Translational research; Laboratory Medicine Radboud University Medical CenterAbstract
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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- Electronic publications [132296]
- Faculty of Medical Sciences [93198]
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