Peripheral Treatment with Enoxaparin, a Low Molecular Weight Heparin, Reduces Plaques and β-Amyloid Accumulation in a Mouse Model of Alzheimer's Disease

Luigi Bergamaschini, Emanuela Rossi, Claudio Storini, Simone Pizzimenti, Maria Distaso, Carlo Perego, Ada De Luigi, Carlo Vergani, Maria Grazia De Simoni

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)4181-4186
Number of pages6
JournalJournal of Neuroscience
Volume24
Issue number17
DOIs
Publication statusPublished - Apr 28 2004

Keywords

  • Alzheimer
  • Amyloid
  • APP23 mouse
  • Binding agent
  • Complement system
  • Heparin
  • Inflammation
  • Kinin system
  • Low molecular weight heparin

ASJC Scopus subject areas

  • Neuroscience(all)

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