The study addresses a gap in current medical capabilities, as there is no treatment available today to stop the death of brain cells in neurodegenerative diseases known as tauopathies, including Alzheimer's disease. In these conditions, twisted clumps of a protein called tau accumulate in the brain, leading to progressive cognitive decline.

David M. Holtzman, the Barbara Burton and Reuben M. Morriss III Distinguished Professor in WashU Medicine's Department of Neurology, served as the senior author of the research. Joshua T. Emmerson, a postdoctoral researcher in Holtzman's lab, was the first author of the Neuron study. He also directs WashU's Hope Center for Neurological Disorders and the Knight Alzheimer Disease Research Center at WashU Medicine. "If we can show that we're really decreasing brain cell death, it's certainly worth trying to pursue that pathway to prevent the most devastating consequences of these diseases," he said.

The research team injected young mice with tau buildup with an antibody that blocked CXCR3 every five days for three and a half months. This intervention targeted the protein CXCR3, which acts as a receptor on T cells. Injecting mice with an antibody to the protein CXCR3 over several months blocked the route used by T cells to enter the brain, reducing the number of those cells in the brain by about half.

Testing revealed that the antibody traveled to the border of each animal's brain but not into the brain tissue. Despite not entering the central nervous system directly, the treated animals had less evidence of nerve cell damage compared with untreated mice. Treated mice kept roughly 40% more tissue in memory centers of the brain compared with untreated mice. Additionally, treated mice performed better on a memory test compared with untreated mice.

The levels of tau in the brains of treated and untreated mice did not change, indicating that the therapeutic effect occurred independently of tau clearance. "For this therapeutic approach, if it is safe, you wouldn't have to design the drug to get into the brain - which is a big deal since most molecules don't cross the blood-brain barrier well - and you don't have to get rid of the tau to get this therapeutic effect," he said.

This approach contrasts with existing treatments. The two existing Alzheimer's drugs on the market, lecanemab and donanemab, target a protein called amyloid. Anti-amyloid medications can slow a person's decline but haven't been shown to keep brain cells from dying.

Furthermore, anti-amyloid medications do not work against primary tauopathies. Alzheimer's is a secondary tauopathy in which both amyloid and tau proteins accumulate.

The study builds on prior work by the same laboratory. In 2023, Holtzman’s lab published a study in Nature demonstrating that T cells contribute to neurodegeneration in tauopathy models, establishing a precedent for targeting immune pathways to address Alzheimer’s pathology. WashU Medicine’s Department of Neurology has a history of pioneering research on blood-brain barrier dynamics, including David M. Holtzman’s earlier work on how immune cells access the brain, which informed the 2026 study’s focus on CXCR3 blockade.

"Until not that long ago, most people, including myself, did not think that the immune response was even involved in neurodegenerative diseases that are due to protein accumulation in the brain," he said. He added that the identification of these cellular mechanisms opens new avenues for intervention. "That these dendritic cells are involved in neurodegenerative disease is exciting; we've shown they're important, and that they are a potential target for future therapy."

Why It Matters

The absence of treatments that halt neurodegeneration in tauopathies represents an unmet medical need. By demonstrating that blocking T-cell entry reduces brain tissue loss without altering tau levels, the study suggests that immune modulation outside the blood-brain barrier can protect neurons. This finding challenges the conventional view that therapies must penetrate the brain to be effective against neurodegenerative proteins.

The research connects immune signaling in lymph nodes to brain health, offering a specific target in the CXCR3 pathway. With existing T-cell manipulation therapies approved for other conditions, this pathway may allow for faster translation to clinical trials than entirely novel drug classes.

Timeline

The study on immune pathways outside the brain was published September 3 in Nature Neuroscience. The Neuron study on CXCR3 blockade in tauopathies was assigned a DOI (10.1016/j.neuron.2026.08.030) and published on September 28, 2026, confirming its status as a peer-reviewed primary document. Researchers at Washington University School of Medicine in St. Louis found a potential way to block part of the immune response and prevent resulting damage in tauopathies. The findings on CXCR3 blockade appeared September 28 in the journal Neuron.

What's New

There is no treatment available today to stop the death of brain cells in neurodegenerative diseases known as tauopathies, including Alzheimer's disease. In tauopathies, twisted clumps of a protein called tau accumulate in the brain.

He stated that one of the issues in developing treatments for neurological diseases is that you need to engineer your treatment so that it gets into the brain and past the blood-brain barrier, but we might not actually need to get the drugs into the central nervous system to mitigate neurodegeneration. He also noted that there are lots of ways to manipulate T cells that have been studied extensively and that are approved treatments for other diseases, but many haven't yet been explored for neurodegenerative diseases. He said that in tauopathies, including Alzheimer's disease, there's no treatment right now that actually decreases neurodegeneration.

How Sources Differ

Researchers found details regarding the mechanism of T-cell involvement that differ between publications. The Neuron journal article states that researchers found that in mice lacking the CXCL10 chemokine or the receptor protein CXCR3 on T cells, T cells did not infiltrate the brain. The Nature Neuroscience journal article states that in experiments with mice, researchers found that T cells receive signals from lymph nodes that appear to prepare them to enter the brain and contribute to damage.

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