Powerful beneficial effects of macrophage colony-stimulating factor on -amyloid deposition and cognitive impairment in Alzheimer's disease
BrainPublished 21 May 2008
Vincent Boissonneault, Mohammed Filali, Maryse Lessard, Jane K. Relton, Gordon Tin Chun Wong, Serge Rivest
Citations218
SJR quartileQ1
SJR score4.72
SNIP2.85
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TL;DR
It is shown that injecting macrophage colony-stimulating factor to Swedish beta-amyloid precursor protein (APP(Swe)/PS1 transgenic mice on a weekly basis prior to the appearance of learning and memory deficits prevented cognitive loss and provided compelling evidence that systemic M-CSF administration is a powerful treatment to stimulate bone marrow-derived microglia, degrade Abeta and prevent or improve the cognitive decline associated with Abeta burden in a mouse model of Alzheimer's disease.
Abstract
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 beta-amyloid (Abeta) in both soluble and aggregate forms. Here, we show that injecting macrophage colony-stimulating factor (M-CSF) to Swedish beta-amyloid precursor protein (APP(Swe))/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 Abeta 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 Abeta in the brain of M-CSF-treated animals and the phagocytosed peptides were located in the late endosomes and lysosomes. Less Abeta(40) and Abeta(42) monomers were also detected in the extracellular protein enriched fractions of M-CSF-treated transgenic mice when compared with vehicle controls. Finally, treating APP(Swe)/PS1 mice that were already demonstrating installed Abeta 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 Abeta and prevent or improve the cognitive decline associated with Abeta burden in a mouse model of Alzheimer's disease.
Keywords
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