Microglia Demonstrate Local Mixed Inflammation and a Defined Morphological Shift in an APP/PS1 Mouse Model

Abstract

Microglia are traditionally described as the immune cells of the brain and have an inflammatory role in Alzheimer's disease (AD). Microglial morphological and phenotypic shifts in AD have not been fully characterized; however, microglia are often described as either pro- or anti-inflammatory. To determine microglial if microglial morphology and phenotype changes with disease status. This study observed morphology through Iba1 immunohistochemistry on tissue sections encompassing the primary motor cortex and somatosensory barrel fields. Immunohistochemistry for pro-inflammatory markers: CD14 and CD40; and anti-inflammatory markers: CD16 and TREM2, was performed at 3, 6, and 12 months of age which correlated with pre-plaque, onset, and significant plaque load in APP/PS1 brains (n = 6) and compared to age-matched littermate controls (n = 6). Microglia demonstrated a defined morphological shift with time. Deramified morphologies increased in the APP/PS1, at both 6 months (p < 0.0001) and 12 months (p < 0.0001). At 12 months, there were significantly lower numbers of ramified microglia (p < 0.001). Results indicated that microglia have a heterogenic marker immunoreactivity as CD16, TREM2, and CD40 were associated with an activated morphology at the same time points. All inflammatory markers were significantly upregulated at 12 months in the APP/PS1 mice (TREM2 (F(2,30) = 10.75, p = 0.0003), CD40 (F(2,30) = 15.86, p < 0.0001), CD14 (F(2,30) = 6.84, p = 0.0036), and CD16 (F(2,30) = 3.026, p = 0.0635)). Our data indicate that pro- and anti-inflammatory factors of microglia occur in APP/PS1 mice.