Peripheral Treatment with Enoxaparin, a Low Molecular Weight Heparin, Reduces Plaques and β-Amyloid Accumulation in a Mouse Model of Alzheimer's Disease
Open Access
- 28 April 2004
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 24 (17) , 4181-4186
- https://doi.org/10.1523/jneurosci.0550-04.2004
Abstract
We investigated the effect of long-term, peripheral treatment with enoxaparin, a low molecular weight heparin, in transgenic mice overexpressing human amyloid precursor protein751. Enoxaparin (6 IU per mouse intraperitoneally, three times a week for 6 months) significantly lowered the number and the area occupied by cortical β-amyloid deposits and the total β-amyloid (1-40) cortical concentration. Immunocytochemical analysis of glial fibrillary acid protein-positive cells showed that enoxaparin markedly reduced the number of activated astrocytes surrounding β-amyloid deposits.In vitro, the drug dose-dependently attenuated the toxic effect of β-amyloid on neuronal cells. Enoxaparin dose-dependently reduced the ability of β-amyloid to activate complement and contact systems, two powerful effectors of inflammatory response in AD brain. By reducing the β-amyloid load and cytotoxicity and proinflammatory activity, enoxaparin offers promise as a tool for slowing the progression of Alzheimer's disease.Keywords
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