Border-Associated Macrophage Migrasomes In Alzheimer’S Disease: An Emerging Aβ-Senescence-Microglia Axis?
Our brains have special immune cells, called border-associated macrophages (BAMs), located at the brain’s edges. These cells are crucial for keeping the brain healthy, helping to clear waste like amyloid-beta (Aβ) and maintaining blood vessel function. However, new research suggests that as we age and Aβ builds up, these BAMs can become stressed and enter a state of “senescence,” meaning they stop functioning properly and can even harm surrounding cells.
One key way these senescent BAMs might cause trouble is by releasing tiny packages called migrasomes. Think of migrasomes as small bubbles that pinch off from cells, carrying various molecules and signals. In this context, BAMs, particularly when exposed to a specific type of Aβ (Aβ40), produce migrasomes enriched with certain proteins. These migrasomes can then travel and deliver their cargo to other brain cells, including microglia, which are the brain’s primary immune cells.
When microglia receive these migrasomes from senescent BAMs, they too can become dysfunctional, resisting programmed cell death and entering a senescent-like state themselves. This creates a harmful cycle: compromised BAMs lead to compromised microglia, which further impairs the brain’s ability to clear Aβ, damages blood vessels, and fuels inflammation. This ongoing damage can contribute to the progression of conditions like Alzheimer’s disease.
Understanding this communication pathway between BAMs and microglia via migrasomes opens up new avenues for potential treatments. If we can find ways to prevent BAMs from becoming senescent or block the release or uptake of these harmful migrasomes, we might be able to interrupt this damaging cycle and protect brain health during aging.
Source: link to paper