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 protein(751). Enoxaparin (6 IU per mouse intraperitoneally, three times a week for 6 months) significantly lowered the number and the area occupied by cortical beta-amyloid deposits and the total beta-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 beta-amyloid deposits. In vitro, the drug dose-dependently attenuated the toxic effect of beta-amyloid on neuronal cells. Enoxaparin dose-dependently reduced the ability of beta-amyloid to activate complement and contact systems, two powerful effectors of inflammatory response in AD brain. By reducing the beta-amyloid load and cytotoxicity and proinflammatory activity, enoxaparin offers promise as a tool for slowing the progression of Alzheimer's disease.
Bergamaschini
Luigi
L
Department of Internal Medicine, Ospedale Maggiore, Instituto di Ricovero e Cura a Carattere Scientifico, University of Milan, 20122 Milan, Italy. luigi.bergamaschini@unimi.it
Rossi
Emanuela
E
Storini
Claudio
C
Pizzimenti
Simone
S
Distaso
Maria
M
Perego
Carlo
C
De Luigi
Ada
A
Vergani
Carlo
C
De Simoni
Maria Grazia
MG
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003167:Complement Activation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity; D058225:Plaque, Amyloid / Q000187:drug effects* / Q000473:pathology; D051381:Rats
D016229:Amyloid beta-Peptides; D017984:Enoxaparin; D005904:Glial Fibrillary Acidic Protein; D006495:Heparin, Low-Molecular-Weight; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)