Examining the immunomodulatory effects of GM‐CSF and IL‐12 in a mouse model of Alzheimer’s disease (728.2)

Abstract

Granulocyte macrophage colony stimulating factor (GM‐CSF), a growth factor for microglia/macrophages, has been associated with protective functions in a mouse model of Alzheimer's disease (AD) in terms of Amyloid β (Aβ) plaque accumulation and cognitive function. We extended these studies by combining GM‐CSF and Interleukin‐12 (IL‐12), considered to be a differentiation factor of naive T‐cells into Th1 cells. A transgenic APPswe/PS1dE9 mouse model for AD was used and mice were grown to an advanced stage of brain Aβ plaque deposition. At 18 months old, AD mice were then injected daily for 20 days, subcutaneously with doses of GM‐CSF (1.7 μg/day) and/or IL‐12 once a week (20 ng) and sacrificed at day 21. Mice were divided into the following groups: 1) AD mice with GM‐CSF plus IL‐12, 2) AD mice with IL‐12 alone and 3) AD mice with no treatment. Mouse brains were perfused and brain slices were quantitated by immunohistochemical methods using Aperio software for Aβ 1‐40 or Aβ 1‐42 peptides. The results indicate a complex neuromodulatory effect. Aβ 1‐40 demonstrated a modest decrease in the AD, GM‐CSF, IL‐12 group compared to the control AD group. However, Aβ 1‐40 was highly variable in the AD, IL‐12 group compared to the control AD group. Aβ 1‐42 on the on the other hand, was significantly decreased in the AD, IL‐12 group, compared to the AD control group. However, there was no significant change in Aβ 1‐42 in the AD, GM‐CSF, IL‐12 group. Analysis of microglial activation in these samples is ongoing and final results will be presented.