Stem cell factor and granulocyte-colony stimulating factor inhibit amyloid-beta deposition and improve cognitive function in APP/PS1 transgenic mice

Abstract

Alzheimer's disease (AD), the major cause of dementia, is a serious problem in both public health and financial burdens in the US. Currently, no treatment can stop the progress of this devastating disease. Substantial evidence has shown that amyloid beta (Aβ) peptide plays a critical role in AD. We have previously reported that stem cell factor (SCF) in combination with granulocyte-colony stimulating factor (G-CSF) (SCF+G-CSF) enhancs entry of bone marrow-derived cells (BMDCs) into the brain of chronic stroke and improves functional outcome in chronic stroke. Here we determined whether SCF+G-CSF treatment inhibited Aβ deposits and improved cognitive function in a mouse model of AD (APP/PS1). To track BMDCs, bone marrow harvested from the mice carrying green fluorescent protein (GFP) was transplanted to the APP/PS1 mice. Thereafter, SCF+G-CSF were subcutaneous administered for 12 days, beginning at the age of 8 months when Aβ plaques had appeared in the brain. To evaluate special learning and memory, water maze test was performed before and 9 months after treatment. We observed that SCF+G-CSF-treated mice showed significantly shorter escape latency and that the number of senile plaques was significantly reduced by SCF+G-CSF treatment. In addition, a significant high number of GFP+/Iba1+ cells surrounding Aβ plaques was seen in SCF+G-CSF-treated mice. These data suggest that SCF+G-CSF treatment may delay AD progress by enhancing clearance of Aβ deposits via BM-derived microglial cells. These data would help in developing an effective treatment to improve health of AD.