Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Brain (London, England : 1878), 2009-04, Vol.132 (4), p.1078-1092

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2009

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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.