Astrocyte signal loss in Alzheimer’s disease

Awake mice with hallmarks of Alzheimer’s disease show disruptions in the way some of their supporting brain cells respond to the signalling molecule norepinephrine.

Astrocytes (green) surrounding an amyloid plaque (blue), a hallmark of Alzheimer’s disease. Image credit: Åbjørsbråten, Skaaraas et al. (CC BY 4.0)

Neurodegenerative conditions such as Parkinson’s or Alzheimer’s disease are characterized by neurons dying and being damaged. Yet neurons are only one type of brain actors; astrocytes, for example, are star-shaped ‘companion’ cells that have recently emerged as being able to fine-tune neuronal communication. In particular, they can respond to norepinephrine, a signaling molecule that acts to prepare the brain and body for action. This activation results, for instance, in astrocytes releasing chemicals that can act on neurons.

Certain cognitive symptoms associated with Alzheimer’s disease could be due to a lack of norepinephrine. In parallel, studies in anaesthetized mice have shown perturbed astrocyte signaling in a model of the condition. Disrupted norepinephrine-triggered astrocyte signaling could therefore be implicated in the symptoms of the disease. Experiments in awake mice are needed to investigate this link, especially as anesthesia is known to disrupt the activity of astrocytes.

To explore this question, Åbjørsbråten, Skaaraas et al. conducted experiments in naturally behaving mice expressing mutations found in patients with early-onset Alzheimer’s disease. These mice develop hallmarks of the disorder. Compared to their healthy counterparts, these animals had reduced astrocyte signaling when running or being startled. Similarly, a fluorescent molecular marker for norepinephrine demonstrated less signaling in the modified mice compared to healthy ones.

Over 55 million individuals currently live with Alzheimer’s disease. The results by Åbjørsbråten, Skaaraas et al. suggest that astrocyte–norepinephrine communication may be implicated in the condition, an avenue of research that could potentially lead to developing new treatments.