Powerful beneficial effects of macrophage colony-stimulating factor on beta-amyloid deposition and cognitive impairment in 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.

• Authors: Vincent Boissonneault, Mohammed Filali, Martine Lessard, Jane Relton, Gordon Wong, Serge Rivest
• Journal: Brain : a journal of neurology (Brain) Vol. 132 Issue Pt 4 Pg. 1078-92 (Apr 2009) ISSN: 1460-2156 [Electronic] England
• PMID: 19151372 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Macrophage Colony-Stimulating Factor

Topics

• Alzheimer Disease (drug therapy, metabolism, pathology, psychology)
• Amyloid beta-Peptides (metabolism)
• Animals
• Behavior, Animal (drug effects)
• Brain (metabolism)
• Cognition Disorders (etiology, metabolism, pathology, prevention & control)
• Disease Models, Animal
• Disease Progression
• Drug Evaluation, Preclinical (methods)
• Endosomes (metabolism)
• Macrophage Colony-Stimulating Factor (therapeutic use)
• Male
• Mice
• Mice, Transgenic
• Microglia (pathology)