FDA-approved drug may slow brain cell death in Alzheimer’s patients

Long before memory problems appear, your brain may already be losing neurons. That is the unsettling message from new work by scientists at the University of Colorado Anschutz Medical Campus, who found that signs of brain cell injury begin in early life and rise sharply with age.

In a study, the team tracked proteins in blood that spill out when neurons are damaged or die. Two of these markers, called UCH-L1 and NfL, were very low in children and young adults. Their levels climbed every year, then rose exponentially up to about age 85.

Early in life, those changes likely reflect normal aging. Later on, the same markers appear to signal trouble. High levels of UCH-L1 in older adults were linked with worse outcomes, suggesting that the quiet loss of neurons may already be affecting thinking and memory.

The researchers also measured another protein, GFAP, which rises with brain inflammation. They found that GFAP in blood increases noticeably starting around age 40, and that both GFAP and UCH-L1 run higher in women, for reasons that are still unclear.

“These findings suggest that the exponentially higher levels of these markers with age, likely accelerated by neuroinflammation, may underlie the contribution of aging to cognitive decline and AD and that sargramostim treatment may halt this trajectory,” said senior author Huntington Potter, PhD, who directs the University of Colorado Alzheimer’s and Cognition Center.

The hopeful part of this story is that the same study points to a possible way to slow that damage. The team focused on sargramostim, also known by the brand name Leukine, a lab made version of the natural human protein GM-CSF. Doctors have used it for about 30 years to help people recover immune cells after cancer treatment and in other conditions.

In animal models, GM-CSF has done more than boost the immune system. Potter said, “GM-CSF also reverses cognitive decline and the rate of neuron death after just a few weeks of treatment.” Those results raised a simple but bold question. If the drug could rescue brain cells in animals, could it help people living with Alzheimer’s disease.

The team had already carried out a first clinical trial in people with mild to moderate Alzheimer’s. In that small study, sargramostim improved blood biomarkers tied to brain pathology while participants were taking it. The biological benefits faded after treatment stopped, but one measure of memory on a cognitive test stayed better for longer.

“This drug improved one measure of cognition and reduced a blood measure of neuron death in people with AD in a relatively short period of time in its first clinical trial,” Potter said.

In the new report, co authored by Stefan Sillau, PhD, Christina Coughlan, PhD, Md. Mahiuddin Ahmed, PhD, and colleagues, the researchers looked more closely at how sargramostim affected neuron death markers. They saw something striking.

“When people with AD were given sargramostim in the clinical trial, their blood levels of the UCH-L1 measure of neuronal cell death dropped by 40% - in our study, this was similar to levels seen in early life,” Potter said. “We were very surprised.”

That large drop hints that the drug temporarily slowed the rate at which neurons were dying. For someone with Alzheimer’s, any slowdown in neuron loss could mean more time with clearer thinking and better daily function.

Sargramostim also led to improved scores on the Mini Mental State Exam, a common screening test used in clinics to check basic cognitive skills. People who received the drug did better on that test compared with those on placebo. Other more detailed cognitive tests did not change, so the benefit appears modest and focused.

At the 45 day follow up after treatment ended, the good news came with a twist. Blood levels of UCH-L1 had returned to pretreatment values, suggesting that neuron death had sped back up. The MMSE scores, however, still showed an advantage for the treated group. That split raises new questions about how long treatment must continue and how biology and behavior relate over time.

"The age spanning analysis of UCH-L1, NfL and GFAP is more than a side note. It hints at a way to catch harmful brain changes earlier in life. If rising neuron death markers can be measured in a simple blood test, doctors may one day spot people on a fast track toward cognitive decline long before symptoms appear," Potter explained to The Brighter Side of News.

"The pattern our team found is sobering. From youth through late adulthood, UCH-L1 and NfL increase steadily, then sharply. GFAP jumps starting in midlife and stays elevated. Higher values in women suggest that sex specific biology may shape brain aging and Alzheimer’s risk," he continued.

For you, this means that neuron loss is not just an end stage event. It is a lifelong process, probably pushed along by inflammation. In that context, sargramostim’s role as an immune modulator is important. The natural GM-CSF protein stimulates the bone marrow to make new immune cells and also affects immune cells in the brain. Those actions may help clear harmful debris and tune down damaging inflammation.

The new data suggest that by dialing down inflammation and supporting the brain’s cleanup systems, sargramostim can bring a key marker of neuron death closer to levels seen in much younger people, at least for as long as the drug is on board.

The authors are careful not to oversell their results. They stress that changes in blood markers happen throughout life as a normal part of aging. A single small trial cannot prove that a drug will slow Alzheimer’s disease in the long run.

Whether sargramostim needs to be given continuously, in repeated courses, or only at certain stages is unknown. The early signal on the MMSE needs to be confirmed in larger groups and matched to real world outcomes, such as how long people can live independently.

A second, longer and more extensive clinical trial of sargramostim in people with mild to moderate Alzheimer’s is already under way. That study will follow participants for a longer time and will look more closely at memory, daily function and safety.

Until those results are in, Potter and his co authors urge caution. They note that sargramostim “should not be prescribed or taken for any non-approved use” until regulators such as the FDA review complete data and make a formal decision.

For now, the work offers something rare in Alzheimer’s research: a sense that the trajectory of neuron loss might be shifted, not just watched. It also reminds you that the brain’s decline with age is not simple fate; it is biology, with signals that can be measured and, perhaps one day, meaningfully changed.

If future trials confirm these findings, sargramostim or similar drugs could become part of a new strategy for treating Alzheimer’s disease. Instead of waiting for memory loss to become severe, doctors might use blood markers like UCH-L1, NfL and GFAP to identify people at high risk and intervene earlier.

For patients and families, that could mean more years of preserved independence and clearer thinking. For researchers, the markers provide tools to test whether new treatments are slowing neuron loss long before large clinical changes appear.

The work also deepens the link between inflammation, normal aging and Alzheimer’s. By showing that inflammation related proteins such as GFAP rise in midlife and are higher in women, the study points to potential windows where lifestyle changes or future drugs could support brain health, even outside of diagnosed disease.

Finally, the fact that sargramostim has decades of use in other conditions may speed its path if it proves effective. Repurposed drugs often move faster through the approval process because their basic safety is already known. That could bring helpful treatments to people sooner, especially if blood tests allow precise targeting to those most likely to benefit.

Research findings are available online in the journal Cell Reports Medicine.

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