Journal Article

Powerful beneficial effects of macrophage colony-stimulating factor on β-amyloid deposition and cognitive impairment in Alzheimer's disease

Vincent Boissonneault, Mohammed Filali, Martine Lessard, Jane Relton, Gordon Wong and Serge Rivest

in Brain

Published on behalf of The Guarantors of Brain

Volume 132, issue 4, pages 1078-1092
Published in print April 2009 | ISSN: 0006-8950
Published online January 2009 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awn331
Powerful beneficial effects of macrophage colony-stimulating factor on β-amyloid deposition and cognitive impairment in Alzheimer's disease

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Alzheimer's disease is a major cause of dementia in humans. The appearance of cognitive decline is linked to the overproduction of a short peptide called β-amyloid (Aβ) in both soluble and aggregate forms. Here, we show that injecting macrophage colony-stimulating factor (M-CSF) to Swedish β-amyloid precursor protein (APPSwe)/PS1 transgenic mice, a well-documented model for Alzheimer's disease, on a weekly basis prior to the appearance of learning and memory deficits prevented cognitive loss. M-CSF also increased the number of microglia in the parenchyma and decreased the number of Aβ deposits. Senile plaques were smaller and less dense in the brain of M-CSF-treated mice compared to littermate controls treated with vehicle solution. Interestingly, a higher ratio of microglia internalized Aβ in the brain of M-CSF-treated animals and the phagocytosed peptides were located in the late endosomes and lysosomes. Less Aβ40 and Aβ42 monomers were also detected in the extracellular protein enriched fractions of M-CSF-treated transgenic mice when compared with vehicle controls. Finally, treating APPSwe/PS1 mice that were already demonstrating installed Aβ pathology stabilized the cognitive decline. Together these results provide compelling evidence that systemic M-CSF administration is a powerful treatment to stimulate bone marrow-derived microglia, degrade Aβ and prevent or improve the cognitive decline associated with Aβ burden in a mouse model of Alzheimer's disease.

Keywords: Alzheimer's disease; β-amyloid; microglia; M-CSF

Journal Article.  7999 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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