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

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Microglia, the brain's immune cells, are implicated in Alzheimer's disease (AD) pathogenesis, traditionally viewed with an inflammatory role.
• The dynamic morphological and phenotypic alterations of microglia in AD remain incompletely understood, with ongoing debate on their pro- or anti-inflammatory nature.

Purpose of the Study:

• To investigate the changes in microglial morphology and phenotype in relation to disease progression in a mouse model of Alzheimer's disease.
• To correlate microglial activation markers with specific disease stages, including pre-plaque, onset, and significant plaque load.

Main Methods:

• Utilized Iba1 immunohistochemistry to assess microglial morphology in the primary motor cortex and somatosensory barrel fields of APP/PS1 mice and age-matched controls.
• Performed immunohistochemistry for pro-inflammatory markers (CD14, CD40) and anti-inflammatory markers (CD16, TREM2) at 3, 6, and 12 months of age.

Main Results:

• Observed a significant increase in deramified microglial morphologies in APP/PS1 mice at 6 and 12 months, with a decrease in ramified microglia at 12 months.
• Demonstrated heterogeneous marker immunoreactivity, with CD16, TREM2, and CD40 associated with activated morphology.
• Found significant upregulation of all inflammatory markers (TREM2, CD40, CD14, CD16) at 12 months in APP/PS1 mice compared to controls.

Conclusions:

• Microglial response in the APP/PS1 Alzheimer's disease model is complex, exhibiting both pro- and anti-inflammatory marker expression.
• Morphological changes in microglia are evident and correlate with disease progression and inflammatory marker upregulation.