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

Enoxaparin (Enox), a low molecular weight heparin, has been shown to lower brain amyloid β (Aβ) 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 Aβ levels in the APPswe/PS1dE9 mouse model by giving injections at an early (starting at 5months of age) and late (starting at 10 and 12months of age) stage of Aβ 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 Aβ levels at 5months of age, but significantly increased guanidine HCl-extracted Aβ42 and Aβ40 levels in both 10- and 12-month-old mice. In vitro, Enox increased aggregation of Aβ, even when Aβ was pre-aggregated.