Peripheral treatment with enoxaparin, a low molecular weight heparin, reduces plaques and beta-amyloid accumulation in a mouse model of Alzheimer's disease

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.