A Simple Blood Test Could Detect the Risk of Alzheimer’s Years in Advance

Neutrophils, a type of white blood cell that circulates in the bloodstream, are among the body’s first lines of defense against infections and inflammation. When the immune system is activated, their numbers can rise rapidly, altering the balance between neutrophils and other immune cells. Doctors can measure this balance using a standard laboratory value known as the neutrophil-to-lymphocyte ratio (NLR). This value is routinely determined from a complete blood count, a common test used to detect infections and assess immune health. New research from NYU Langone Health suggests that this simple measurement may do more than just reflect a person’s current state of health. It could also help identify individuals at increased risk of developing Alzheimer’s and related forms of dementia even before symptoms appear. The study analyzed NLR data from nearly 400,000 patients across two large healthcare systems.

Large-scale Study Links Immune Cells to Dementia Risk

“Our study is the first large-scale investigation to show that neutrophil levels are associated with an increased risk of dementia in humans,” said the study’s lead author, Dr. Tianshe (Mark) He, a data scientist in the Department of Psychiatry at NYU Grossman School of Medicine. “An increase in neutrophils occurs even before any signs of cognitive decline, which provides a compelling argument for investigating whether neutrophils actively contribute to disease progression.” Dr. He and co-senior author Jaime Ramos-Cejudo, PhD, assistant professor in the departments of psychiatry and neurology at NYU Grossman School of Medicine, are both affiliated with the Cooperative Studies Program at the VA Boston Healthcare System.

The study, published in “Alzheimer’s & Dementia,” included data from approximately 285,000 patients treated at four NYU Langone hospitals, as well as from about 85,000 individuals from the Veterans Health Administration. To ensure accuracy, the team used the earliest eligible NLR measurement for each patient. These measurements had to fall within the study period, have been taken at a time when the patients were at least 55 years old, and precede a diagnosis of Alzheimer’s or dementia. The researchers then tracked whether these individuals developed dementia over the course of the study period.

Elevated NLR Linked to Short- and Long-Term Risk

In both groups, higher NLR values were consistently associated with an increased likelihood of developing Alzheimer’s or other forms of dementia. This association held true for both short-term and long-term risk. The researchers defined a “high” NLR based on the median value, meaning that half of the participants had higher values and the other half had lower values.

The analysis also revealed differences among subgroups. Among Hispanic patients, a stronger association was observed between an elevated NLR and the risk of dementia, though it remains unclear whether this is due to genetic influences or social factors such as disparities in access to medical care. An elevated NLR was also associated with a higher risk among women in both healthcare systems.

According to Dr. Ramos-Cejudo, the findings are important for two main reasons. On its own, a high NLR value is likely not a definitive predictor of dementia. However, when combined with other known risk factors, it could help identify individuals who might benefit from closer monitoring, additional testing, or early interventions before cognitive symptoms appear. The findings also support the growing evidence that neutrophils may play a more active role in the disease process itself.

Could Immune Cells Drive the Progression of Alzheimer’s?

Neutrophils are among the immune system’s first line of defense and are normally responsible for quickly fighting infections and repairing damaged tissue. Under certain conditions, however, they can trigger an excessive or misdirected inflammatory response. In the context of Alzheimer’s disease, there is evidence that neutrophils may migrate into the brain and exacerbate inflammatory processes there. Such neutrophil-triggered inflammatory reactions have been observed in both the brain tissue and the blood vessels of affected individuals. Animal models also suggest that these cells may contribute to the progression of the disease, for example by impairing blood flow or indirectly damaging nerve cells.

Aging likely plays an additional role here: As we age, the regulation of the immune system changes, including the mechanisms that break down old or overactive neutrophils. If this “cleanup process” is disrupted, more dysfunctional neutrophils could accumulate, which in turn promotes chronic inflammation and tissue damage—a potential amplifier of neurodegenerative processes. Despite these indications, researchers emphasize that a clear cause-and-effect relationship has not yet been proven. It therefore remains unclear whether neutrophils actively contribute to disease onset or are rather a concomitant feature of already ongoing damage processes. Another difficulty lies in the fact that neutrophils have a very short lifespan and must therefore be examined directly from fresh blood samples. This significantly complicates long-term studies and the precise analysis of their role in disease progression. Overall, current research suggests that neutrophils are a potentially important but not yet fully understood factor in Alzheimer’s pathology—with possible relevance for future therapeutic approaches.

Ongoing Research on Diagnosis and Treatment

Ongoing research is currently attempting to define the role of neutrophils in Alzheimer’s disease much more precisely—particularly with regard to diagnosis and potential therapeutic approaches. Dr. Ramos-Cejudo and his team at the VIDA Laboratory (Laboratory for Vascular and Immunological Dysfunction in Aging and Alzheimer’s) are pursuing an integrative approach: They combine immunological measurements of neutrophil activity with modern brain imaging techniques such as positron emission tomography (PET) and diffusion magnetic resonance imaging, as well as detailed cognitive tests. The goal is to establish connections between inflammatory processes, structural changes in the brain, and actual cognitive decline. A particularly interesting aspect of this research is the question of whether neutrophils merely function as biomarkers—that is, as measurable indicators of disease processes already underway—or whether they actively contribute to deterioration. Should the latter be confirmed, they could become an attractive target for new therapies, such as drugs that regulate their activity or limit their harmful effects in the brain.

At the same time, the so-called neutrophil-to-lymphocyte ratio (NLR) is gaining importance. This ratio, which can be determined relatively easily from blood samples, could establish itself as a cost-effective and easily accessible diagnostic tool. Initial evidence suggests that an altered NLR may be associated with an increased risk of neurodegenerative diseases. In the future, it could therefore help identify individuals at increased risk early on—possibly long before clinically recognizable symptoms appear. This would open the door to early interventions, whether through lifestyle measures or targeted medical therapies. Nevertheless, caution is still warranted here: The results so far are promising, but not yet sufficient to derive clear clinical recommendations. Larger, long-term studies are needed to clarify how reliable these markers actually are and whether interventions targeting neutrophil function can measurably improve disease progression.