Stem cell factor and granulocyte colony-stimulating factor reduce β-amyloid deposits in the brains of APP/PS1 transgenic mice

APP/PS1 transgenic mice were used as the model of AD. To track bone marrow-derived cells in the brain, the bone marrow of the APP/PS1 mice was replaced with the bone marrow from mice expressing green fluorescent protein (GFP). Six weeks after bone marrow transplantation, mice were randomly divided into a saline control group and a SCF+G-CSF-treated group. SCF in combination with G-CSF was administered subcutaneously for 12 days. Circulating bone marrow stem cells (CD117+ cells) were quantified 1 day after the final injection. Nine months after treatment, at the age of 18 months, mice were sacrificed. Brain sections were processed for immunohistochemistry to identify β-amyloid deposits and GFP expressing bone marrow-derived microglia in the brain.Systemic administration of SCF+G-CSF to APP/PS1 transgenic mice leads to long-term reduction of β-amyloid deposition in the brain. In addition, we have also observed that the SCF+G-CSF treatment increases circulating bone marrow stem cells and augments bone marrow-derived microglial cells in the brains of APP/PS1 mice. Moreover, SCF+G-CSF treatment results in enhancement of the co-localization of bone marrow-derived microglia and β-amyloid deposits in the brain.These data suggest that bone marrow-derived microglia play a role in SCF+G-CSF-induced long-term effects to reduce β-amyloid deposits. This study provides insights into the contribution of the hematopoeitic growth factors, SCF and G-CSF, to limit β-amyloid accumulation in AD and may offer a new therapeutic approach for AD.Alzheimer's disease (AD) is the major cause of dementia and the sixth leading cause of death in the United States [1]. Currently, no treatment has been proven to stop AD. Although the cause of AD remains uncertain, substantial evidence shows that toxic β-amyloid peptide plays a critical role in the progress of this devastating disease [2].The microglial cells that cluster around β-amyloid plaques had been thought to participate in the pathogenesis of