Microglia prevent peripheral immune cell invasion and promote an anti-inflammatory environment in the brain of APP-PS1 transgenic mice

This research explores the role of microglia, the brain's resident immune cells, in Alzheimer's disease (AD) using a mouse model. By eliminating microglia, the study examines how this affects the infiltration of other immune cells from the body into the brain and the overall inflammatory environment. The study found that removing microglia led to an increase in specific types of immune cells (CD8+ T-cells) entering the brain, suggesting microglia normally prevent these cells from entering. This indicates that microglia may play a role in controlling the brain's immune response in AD. Additionally, the research identified a population of macrophages (another type of immune cell) that are resistant to the treatment used to eliminate microglia. These macrophages were found near amyloid plaques, suggesting they are involved in clearing these plaques in the absence of microglia.

• 1
  PLX5622 treatment successfully reduced microglia numbers but uncovered a treatment-resistant macrophage population (Iba1+/TMEM119−) that strongly expressed the phagocytosis marker CD68 and the lymphocyte activation, homing, and adhesion molecule CD44, specifically at sites of amyloid-beta plaques in the brains of APP-PS1 mice.
• 2
  Ablation of microglia significantly raised the number of CD3+/CD8+ T-cells and reduced the expression of anti-inflammatory genes in the brains of APP-PS1 mice, suggesting microglia might limit CD3+/CD8+ T-cell recruitment.
• 3
  Local macrophages connect innate with adaptive immune responses, potentially serving as a key element in linking innate with adaptive immune responses along AD pathology.