New antibody treatment blocks immune response to prevent Alzheimer's damage

There is no treatment available today to stop the death of brain cells in neurodegenerative diseases known as tauopathies, including Alzheimer's disease, in which twisted clumps of a protein called tau accumulate in the brain. Cells near those clumps begin to die after tau accumulates, but growing evidence suggests that much of the damage doesn't come from the protein directly. Instead, it's the immune system's response to tau that's to blame for the damage that eventually robs people of their memory and independence.

Now, researchers at Washington University School of Medicine in St. Louis have found a potential way to block part of that immune response and prevent the resulting damage. Studying mice with Alzheimer's-like tau accumulation in their brains, the team showed that injecting the animals with an antibody to a protein known as CXCR3 over several months blocked the route used by immune cells known as T cells to get into the brain, reducing the number of those cells in the brain by about half.

Treated mice kept roughly 40% more tissue in memory centers of the brain and did better on a memory test compared with untreated mice - even though the levels of tau in their brains didn't change.

The findings appear Sept. 28 in the journal Neuron.

David M. Holtzman, MD, the Barbara Burton and Reuben M. Morriss III Distinguished Professor in WashU Medicine's Department of Neurology and the study's senior authorIn tauopathies, including Alzheimer's disease, there's no treatment right now that actually decreases neurodegeneration. 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."

How could targeting immune cells fight Alzheimer's?

The two existing Alzheimer's drugs on the market - lecanemab and donanemab - target a protein called amyloid, which forms plaques between brain cells in the early stages of the disease, disrupts cell communication, triggers tau tangles to form inside neurons and eventually leads to cell death. These anti-amyloid medications can slow a person's decline, but they haven't been shown to keep brain cells from dying, and they don't work against primary tauopathies - diseases marked by tau buildup in which amyloid never appears. Alzheimer's is a secondary tauopathy in which both amyloid and tau proteins accumulate.

How T cells got into the brain once activated remained unknown, however. The cells are known to navigate by following chemical trails called chemokines, and Holtzman's team had previously found that one chemokine - called CXCL10 - was elevated in the tau-mouse model they were utilizing. Other groups had shown that CXCL10 was elevated in Alzheimer's. Activated T cells carry a protein on their surface, CXCR3, that follows this particular trail.

The team then injected young mice that had tau buildup in their brains, but hadn't yet had major brain cell loss, with an antibody that blocked CXCR3, administering the treatment every five days for three and a half months. Compared with untreated mice, treated animals had about half as many T cells in their brains at the end of treatment. They also preserved more brain tissue and had less evidence of nerve cell damage. Yet tau tangles appeared the same in treated and untreated animals.

Testing by Holtzman's team revealed that the antibody traveled to the border of each animal's brain but not into the brain tissue - an important finding indicating that neurodegeneration can be treated without having to get a therapy into the brain itself.

A new therapeutic avenue

While more research is needed before the approach could be tested in people, Holtzman noted that existing drugs that target T cells - such as some therapies used for multiple sclerosis and other autoimmune disorders that occur when the body's immune system attacks its own healthy cells - could be evaluated as Alzheimer's therapies, opening a new therapeutic avenue for the disease.

Emmerson JT, Hu H, Savani V, Lin P, Rohde M, Sharma P, Self W, Li Y, Nulman J, Bosch M, Liu Z, Remolina Serrano J, Bao X, Yuede CM, Jorfi M, Tanzi RE, Ulrich JD, Holtzman DM. Peripheral CXCR3 blockade mitigates T cell infiltration and neurodegeneration in a mouse model of tauopathy. Neuron. September 28, 2026. DOI: 10.1016/j.neuron.2026.08.030

This study was supported by a BrightFocus Postdoctoral Fellowship, National Institutes of Health/National Institute on Aging grants R01AG082328 and R01AG085374, the GHR Foundation, the Carol and Gene Ludwig Initiative in Neuroimmunology Research, a gift from Ronald Schaich, a gift from John Ludwig, a gift from Cindy and Evan Goldberg, and the Freedom Together Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

DMH co-founded and is on the scientific advisory board of C2N Diagnostics. DMH is on the scientific advisory boards of Denali, Genentech and Switch, and consults for Pfizer, Roche, Novartis, Annexon and Acta. DMH is on the advisory boards of Neuron and Cell.

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Washington University in St. Louis

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