The Brain’s Immune System and a Breakthrough That Changes Everything

In my recent lectures, podcasts, and blog posts, I’ve been emphasizing a message that is still surprisingly new to many people: the health of the brain is inseparable from the health of its immune system. At the center of that immune system are specialized cells called microglia. This idea—that microglia are not passive bystanders but active decision-makers that shape brain health across the lifespan—is the central theme of my upcoming book, Brain Defenders. For decades, neuroscience focused almost exclusively on neurons. Today, we understand that neurons depend on microglia for protection, repair, and long-term survival.

Microglia are the brain’s resident immune cells. Under healthy conditions, they act as vigilant caretakers. They clear debris, remove damaged cells, support synapses, maintain myelin, and calm inflammation once a threat has passed. In this state, microglia truly defend the brain. But when microglia become dysfunctional—due to genetics, metabolic stress, chronic inflammation, toxins, infections, or aging—they can shift into a destructive mode. Instead of repairing tissue, they promote ongoing inflammation, damage white matter, and accelerate neurodegeneration.

This shift in microglial behavior is now recognized as a key driver of many brain-related conditions, including Alzheimer’s disease, Parkinson’s disease, depression, traumatic brain injury, and the lingering cognitive symptoms seen after viral infections such as COVID-19. In Brain Defenders, I explain how lifestyle choices like diet, exercise, sleep, metabolic health, and environmental exposures strongly influence whether microglia remain protective or become harmful. But an important question remains: what happens when microglia are already severely damaged?

That question is now being answered by a remarkable line of research published in 2025. For the first time in humans, scientists have demonstrated that dysfunctional microglia can be removed and replaced with healthy ones, effectively rebooting the brain’s immune system.

The researchers focused on a rare and devastating genetic brain disease called adult-onset leukoencephalopathy with axonal spheroids and pigmented glia, or ALSP. In this condition, a genetic defect causes microglia to malfunction and gradually disappear. Patients experience progressive cognitive decline, psychiatric symptoms, and loss of motor function. Historically, ALSP has been fatal, with no effective treatment.

Instead of trying to patch or chemically modify the defective microglia, the scientists took a radically different approach. First, they deliberately removed the diseased microglia from the brain. They did this by blocking the survival signals microglia depend on, combined with medical conditioning similar to protocols used in bone marrow transplantation. This created space in the brain by depopulating the malfunctioning immune cells, without damaging neurons.

Next, they allowed new, healthy microglia to take their place. Donor-derived immune precursor cells were introduced into the body. These cells naturally migrated into the brain and differentiated into fully functional microglia. Over time, the new microglia spread throughout the brain, integrated into neural tissue, and resumed normal immune surveillance and repair functions.

The results were striking. In patients who received this treatment, disease progression stopped. Brain imaging stabilized. Cognitive and motor decline halted. In contrast, patients who did not receive treatment continued to deteriorate. This was not a temporary improvement in symptoms. It was a true modification of disease progression.

Why does this matter beyond a rare genetic disorder? Because it proves something fundamental about brain health. It shows that microglia are not merely responding to neurodegeneration; in some cases, they are the primary cause. And it demonstrates that correcting the brain’s immune system can halt neurodegeneration at its source.

This research also opens the door to a completely new way of thinking about treating brain disease. Rather than chasing individual proteins or isolated chemical signals, we can focus on restoring immune balance within the brain. Even more intriguing, scientists are now exploring ways to engineer microglia to be even more protective, allowing them to deliver growth factors, clear toxic proteins, or suppress inflammation long-term. In effect, microglia could become living therapeutic tools inside the brain.

While microglia replacement therapy is still limited to rare diseases and specialized clinical settings, the implications are immediate and personal. This research strongly reinforces the message I’ve been sharing all along: daily choices determine whether microglia defend the brain or damage it. Blood sugar control, insulin sensitivity, exercise, sleep quality, gut health, toxin exposure, and inflammation all shape microglial behavior.

You may never need your microglia replaced. But you absolutely need to support them. That is what Brain Defenders is about: empowering you to keep your brain’s immune system working for you, not against you. This new research does not replace that message. It validates it. And it delivers a powerful takeaway for the future of brain health: even when the brain’s immune system is broken, it may be possible to reset it.