Reparative Effects of Stem Cell Factor and Granulocyte Colony-Stimulating Factor in Aged APP/PS1 Mice

Alzheimer's disease (AD), characterized by the accumulation of β-amyloid (Aβ) plaques and tau neurofibrillary tangles in the brain, neuroinflammation and neurodegeneration, is the most common form of neurodegenerative disease among the elderly. No effective treatment is available now in restricting the pathological progression of AD. The aim of this study is to determine the therapeutic efficacy of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) (SCF+G-CSF) in aged APPswe/PS1dE9 (APP/PS1) mice. SCF+G-CSF was subcutaneously injected for 12 days to 25-month-old male APP/PS1 mice. We observed that SCF+G-CSF treatment reduced the Aβ plaques in both the cortex and hippocampus. SCF+G-CSF treatment increased the association of TREM2⁺/Iba1⁺ cells with Aβ plaques and enhanced Aβ uptake by Iba1⁺ and CD68⁺cells in the brains of aged APP/PS1 mice. Importantly, cerebral expression area of P2RY12⁺and TMEM119⁺ homeostatic microglia and the branches of P2RY12⁺ homeostatic microglia were increased in the SCF+G-CSF-treated aged APP/PS1 mice. SCF+G-CSF treatment also decreased NOS-2 and increased IL-4 in the brains of aged APP/PS1 mice. Moreover, the loss of MAP2⁺dendrites and PSD-95⁺post-synapses and the accumulation of aggregated tau in the brains of aged APP/PS1 mice were ameliorated by SCF+G-CSF treatment. Furthermore, the density of P2RY12⁺ microglia was negatively correlated with Aβ deposits, but positively correlated with the densities of MAP2⁺ dendrites and PSD-95⁺ puncta in the brains of aged APP/PS1 mice. These findings reveal the therapeutic potential of SCF+G-CSF treatment in ameliorating AD pathology at the late stage.