A Natural Immune Protein Drug Shows Potential to Slow Neuron Death in Alzheimer’s Disease
Scientists at the University of Colorado Anschutz Medical Campus have reported findings that could add an intriguing new angle to Alzheimer’s disease research. Their work suggests that a natural immune protein drug, already approved and used for decades in other medical conditions, may help slow neuron death linked to Alzheimer’s disease (AD) and age-related cognitive decline.
The study, published in Cell Reports Medicine, focuses on how neuron damage and death evolve across the human lifespan and how a drug called sargramostim might interrupt this process in people with Alzheimer’s disease. While the results are still preliminary, they raise important questions about early detection, aging-related brain changes, and the possibility of repurposing existing drugs for neurodegenerative conditions.
Neuron Death Begins Earlier Than Many People Realize
One of the most striking aspects of the research is its focus on lifelong changes in the brain, not just what happens in old age. The researchers examined blood samples from people ranging from early childhood to 85 years old. Their goal was to track specific proteins released into the bloodstream when neurons are damaged or die.
Two key biomarkers were central to the study:
- UCH-L1, a protein released when neurons die
- NfL (neurofilament light), a protein released when neurons are damaged
The researchers found that levels of both proteins are very low in early life but increase exponentially with age. This means that neuron damage and death are not sudden events that begin only in old age—they appear to be part of a continuous process that starts much earlier in life.
In younger individuals, these low-level changes likely reflect normal brain aging. However, later in life, higher concentrations of these proteins—particularly UCH-L1—are associated with poorer cognitive outcomes and neurodegenerative disease.
Brain Inflammation Emerges in Midlife
The study also examined a third biomarker: GFAP (glial fibrillary acidic protein). GFAP is a marker of brain inflammation, which is widely believed to play a major role in driving cognitive decline and Alzheimer’s disease.
According to the findings, blood levels of GFAP begin to rise significantly around age 40. This timing is important, as it suggests that neuroinflammation may accelerate decades before clinical symptoms of dementia appear. Inflammation may amplify age-related neuron loss and increase vulnerability to diseases like Alzheimer’s later in life.
Notable Differences Between Men and Women
Another important observation from the study is that women show higher age-related blood levels of UCH-L1 and GFAP than men. The reasons for this difference remain unclear, but it may help explain why women are disproportionately affected by Alzheimer’s disease.
These findings point to the possibility that sex-specific biological processes influence how neurons age and how inflammation contributes to cognitive decline. Understanding these differences could eventually lead to more personalized prevention and treatment strategies.
Sargramostim and the Immune System’s Role in Brain Health
At the center of the study is sargramostim, also known by its brand name Leukine. Sargramostim is a synthetic version of GM-CSF (granulocyte-macrophage colony-stimulating factor), a naturally occurring human protein that stimulates the immune system.
GM-CSF encourages the production of new immune cells in the bone marrow and also influences immune activity in the brain. Sargramostim has been used for about 30 years, primarily to help cancer patients recover white blood cells after chemotherapy and to treat other immune-related conditions.
Previous animal studies showed that GM-CSF could reverse cognitive decline and reduce neuron death within weeks. This prompted researchers to explore whether the drug might have similar effects in people with Alzheimer’s disease.
Results From the First Clinical Trial in Alzheimer’s Patients
In an initial clinical trial involving people with Alzheimer’s disease, sargramostim produced some encouraging results. Participants who received the drug showed a 40% reduction in blood levels of UCH-L1, the biomarker associated with neuron death.
What surprised researchers most was that these reduced levels of UCH-L1 were comparable to levels typically seen in early life, suggesting a meaningful slowdown in neuron loss. However, this effect was temporary. Once the treatment stopped, UCH-L1 levels returned to their pre-treatment values within about 45 days.
Cognitive outcomes were mixed. Participants receiving sargramostim showed improvement on one cognitive test, the Mini-Mental State Examination (MMSE), compared with those taking a placebo. Other cognitive tests did not show significant changes. Interestingly, while the biomarker improvements faded after treatment ended, the MMSE improvement persisted longer, raising questions about how immune modulation affects brain function.
What Remains Unknown
Despite these promising signs, many questions remain unanswered. It is not yet clear whether sargramostim must be taken continuously to maintain its effects on neuron death, or whether longer treatment durations could produce more durable benefits.
Researchers also want to know whether the drug could help slow normal age-related neuron loss, not just Alzheimer’s-related damage. Since blood markers of neuron death increase across the lifespan, this opens the door to exploring whether interventions earlier in life might delay cognitive decline later on.
Importantly, the researchers caution that sargramostim is not approved for treating Alzheimer’s disease, and it should not be used off-label for this purpose until clinical trials are complete and regulatory authorities review the data.
A Larger Trial Is Already Underway
A second, longer, and more comprehensive clinical trial is currently in progress. This study focuses on people with mild-to-moderate Alzheimer’s disease and is designed to better assess safety, cognitive effects, and biological changes over an extended treatment period.
Participants in this ongoing trial are receiving sargramostim or a placebo over several months, along with repeated cognitive assessments, blood and cerebrospinal fluid testing, and brain imaging. The results of this trial will be critical in determining whether sargramostim has real potential as an Alzheimer’s therapy.
Why This Research Matters
Alzheimer’s disease has long been approached primarily through the lens of amyloid plaques and tau tangles. This study highlights a complementary perspective: neuron death, inflammation, and immune system regulation may be equally important targets.
By showing that neuron-death biomarkers rise steadily with age—and can be temporarily reduced by an immune-modulating drug—the research suggests new ways of thinking about early detection, prevention, and treatment. Even if sargramostim itself does not become an approved Alzheimer’s therapy, the insights gained could shape future drug development.
At the very least, this work reinforces the idea that Alzheimer’s disease is not a sudden event, but the result of long-term biological processes that unfold across decades.
Research paper:
https://doi.org/10.1016/j.xcrm.2025.102525
