Inflammation plays a significant role in Alzheimer’s disease (AD), influencing how the condition develops and worsens over time. In the brain, inflammation is not just a simple response to injury or infection; it becomes a complex process involving various immune cells and signaling molecules that can both protect and harm neurons.
One of the key players in this inflammatory process are microglia, which are immune cells residing in the brain. When Alzheimer’s begins, these microglia become activated as they try to clear harmful substances like amyloid-beta plaques—sticky protein clumps that accumulate abnormally in AD. However, this activation can spiral out of control, leading to chronic inflammation that damages neurons instead of protecting them.
Several molecular pathways regulate this neuroinflammation. For example, TREM2 is a receptor on microglia important for managing their response to plaques and controlling inflammation levels. Another critical pathway involves inflammasomes like NLRP3, which trigger production of inflammatory molecules such as interleukins that further fuel brain inflammation and contribute to neuronal damage.
Astrocytes—another type of brain cell involved in supporting neurons—also participate actively in this inflammatory environment. They respond to amyloid-beta by releasing signals that amplify inflammation but also have mechanisms regulated by receptors like AhR (aryl hydrocarbon receptor) which might help reduce harmful effects if properly targeted.
Interestingly, certain genetic mutations can influence how much inflammation occurs during Alzheimer’s progression. For instance, a rare mutation known as the Christchurch mutation reduces inflammatory signaling within brain immune cells by inhibiting specific innate immune pathways such as cGAS-STING. This dampening effect appears protective because it slows down neurodegeneration linked with excessive inflammation.
Moreover, systemic factors outside the brain also connect with AD through shared inflammatory processes seen in diseases like atherosclerosis (hardening of arteries). Chronic low-level systemic inflammation may worsen neuroinflammation inside the brain via complement system activation—a part of innate immunity—which highlights how body-wide health impacts Alzheimer’s risk and progression.
In essence, while some degree of inflammation initially helps clear toxic proteins from the brain during early stages of Alzheimer’s disease, persistent or excessive neuroinflammation driven by activated glial cells ultimately contributes significantly to neuron loss and cognitive decline characteristic of AD. Understanding these intricate interactions between immune responses and neural damage opens new avenues for therapies aimed at calming harmful inflammation without impairing its protective roles within the central nervous system.
