Microglia: The Brain's Immune Cells

Microglia constantly survey the brain, eat debris and invaders, prune unwanted synapses during development — and are now central suspects in Alzheimer's disease and other conditions.

Microglia make up roughly 5–10% of the cells in the brain. Unlike neurons and other glia, which develop from the embryo's nervous tissue, microglia come from the yolk sac early in development and migrate into the brain before the blood-brain barrier closes. They then renew themselves locally throughout life.

Always on patrol

In the healthy brain, microglia were once called "resting". Imaging in living mice in 2005 showed otherwise: their fine branches are in constant motion, sweeping their territory every few hours. When they detect damage — leaked molecules from injured cells, bacteria, abnormal proteins — they rush in, change shape and engulf the debris in a process called phagocytosis.

Sculpting circuits

During development the brain makes far more synapses than it keeps. Microglia help prune them, engulfing synapses tagged by proteins of the complement system, an ancient part of the immune system. Work in mice has shown that synapses that are less active are more likely to be marked and removed — a "use it or lose it" rule carried out by immune cells.

Friends and foes in disease

Many genes that raise the risk of late-onset Alzheimer's disease, such as TREM2, are active mainly in microglia, suggesting these cells play a central role. Microglia can clear amyloid, but chronic activation may also cause harmful inflammation and excessive synapse loss. They are implicated in multiple sclerosis, chronic pain and possibly psychiatric conditions. Variants of the complement gene C4, which affect synaptic pruning, have been associated with schizophrenia risk.