Rochester Reporter

New studies indicate that modulating brain immune cells could help mitigate inflammation associated with Alzheimer's disease. Research suggests that the hormone norepinephrine plays a significant role in this process. This discovery might lead to earlier, more focused treatments tailored for individual patients.

“Norepinephrine is a major signaling factor in the brain and affects almost every cell type. In the context of neurodegenerative diseases such as Alzheimer’s disease, it has been shown to be anti-inflammatory,” explained Ania Majewska, PhD, from the Del Monte Institute for Neuroscience at the University of Rochester, and the senior author of the study published in the journal Brain, Behavior, and Immunity. “In this study, we describe how enhancing norepinephrine’s action on microglia can mitigate early inflammatory changes and neuronal injury in Alzheimer’s models.”

The research, conducted using mice, involved collaboration between two labs focusing on the brain's immune system and Alzheimer's-related inflammation. Linh Le, PhD, a graduate student in both labs, spearheaded the examination of norepinephrine's role. This brain chemical helps manage inflammation through immune cells called microglia, which have a receptor known as β2AR. This receptor regulates the calming of inflammation.

In Alzheimer's and aging, the calming properties of this "switch" become less effective, particularly in brain areas accumulating amyloid plaques. These plaques diminish β2AR receptors on nearby microglia, reducing their inflammation-fighting ability.

The study observed microglia's dynamic, exploratory behavior when influenced by norepinephrine signaling. An image from the research depicted microglial activity, with their cell bodies in white, process extensions in green, and retractions in magenta. The removal or blockage of β2AR receptors worsened brain damage, while their activation reduced detrimental effects. Results varied based on sex and treatment timing.

Traditionally, Alzheimer’s has been considered a result of plaque-induced neural damage. This study highlights the significance of norepinephrine’s calming effect loss on microglia in exacerbating the condition. It also proposes that β2AR receptor issues may start early in the disease, implying that early intervention could be advantageous.

Activating the β2AR receptor reduced inflammation and plaque formation, suggesting future therapies might target this receptor to aid microglia in maintaining an anti-inflammatory state. This could potentially alter the disease’s progression and necessitate personalized treatment, influenced by sex and disease stage.