Norepinephrine (NE) plays a critical role in regulating microglial activity and exhibits anti-inflammatory effects in the brain.

Microglia, the immune cells of the brain, possess b22 adrenergic receptors (b22AR) that help them respond to norepinephrine and mitigate inflammation.

Experiments have shown that blocking b22AR exacerbates brain damage, while stimulating it can reduce harmful effects, highlighting the importance of norepinephrine's calming influence on microglia in managing Alzheimer's disease.

In Alzheimer's disease, the activity of b22AR decreases, particularly in regions affected by amyloid plaques, which leads to heightened neuroinflammation.

A study utilizing a 5xFAD mouse model revealed that the loss of norepinephrine projections occurs prior to neuronal degeneration, with microglia associated with amyloid plaques downregulating b22AR expression early in the disease's progression.

As individuals age, microglia become increasingly inflammatory due to various factors, including inflammatory signals from the immune system, senescent cells, and the buildup of metabolic waste like amyloid-b2.

This age-related increase in microglial inflammation is a contributing factor to neurodegenerative diseases such as Alzheimer's.

Research suggests that issues with b22AR may manifest early in Alzheimer's pathology, indicating that early intervention could be advantageous for treatment.

Microglia are essential for neuroinflammation and synaptic maintenance, functioning similarly to macrophages in the body.