Enoxaparin treatment administered at both early and late stages of amyloid β deposition improves cognition of APPswe/PS1dE9 mice with differential effects on brain Aβ levels.

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.

• Authors: Nienke M Timmer, Laura van Dijk, Catharina E E M van der Zee, Amanda Kiliaan, Robert M W de Waal, Marcel M Verbeek
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 40 Issue 1 Pg. 340-7 (Oct 2010) ISSN: 1095-953X [Electronic] United States
• PMID: 20600909 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2010 Elsevier Inc. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Enoxaparin

Topics

• Alzheimer Disease (drug therapy, metabolism)
• Amyloid beta-Peptides (antagonists & inhibitors, biosynthesis, metabolism)
• Animals
• Cognition Disorders (drug therapy, metabolism)
• Disease Models, Animal
• Enoxaparin (pharmacology, therapeutic use)
• Female
• Humans
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Plaque, Amyloid (drug therapy, metabolism)