Researchers used the 5xFAD Alzheimer’s mouse model to study microglial β2 adrenergic receptor (β2AR) signaling. They found that activating β2AR with norepinephrine agonists lowered neuroinflammation, amyloid plaque accumulation, and neuritic damage, while receptor blockade worsened pathology, identifying β2AR as a potential early therapeutic target.

Key points

• Microglial β2AR expression decreases early in 5xFAD cortex, especially near plaques.
• Blockade of β2AR worsens amyloid load, inflammation, and neuritic damage.
• β2AR stimulation via agonists reduces plaque burden and attenuates neuroinflammation.
• Early loss of cortical norepinephrine projections precedes microglial β2AR downregulation.
• Study validates β2AR-mediated noradrenergic modulation of microglia as therapeutic target.

Why it matters: By highlighting microglial β2AR as a modifiable switch in Alzheimer’s neuroinflammation, this work shifts focus from direct amyloid clearance to immune regulation. Early targeting of this pathway could enhance disease-modifying therapies and outperform existing approaches by intervening before extensive neuronal damage occurs.