No treatment today actually stops brain cells from dying in tauopathies, the group of neurodegenerative diseases that includes Alzheimer’s, where clumps of tau protein build up inside neurons. A growing body of evidence suggests a lot of that damage comes not from the tau itself, but from the immune system’s response to it. A new study in Neuron, from researchers at Washington University in St. Louis, tested a way to blunt that immune response from outside the brain entirely.

The researchers worked with mice engineered to accumulate Alzheimer’s-like tau buildup, starting treatment while the animals were still young and had little brain cell loss. Over roughly three and a half months, the mice received injections — into the body, not the brain — of an antibody blocking CXCR3, a receptor that T cells use to home in on a chemical signal called CXCL10 and follow it into the brain.

The treated mice ended up with roughly half as many T cells in their brains. They retained about 40 percent more tissue in their memory centers, showed less nerve cell damage, and performed better on memory tests, even though their underlying tau levels didn’t change. Mice genetically lacking CXCL10 or CXCR3 showed little T cell infiltration even when researchers deliberately provoked inflammation, reinforcing that this particular signaling pathway, rather than inflammation generally, was doing the damage. Notably, the antibody itself never crossed into the brain tissue — it worked by reaching the brain’s outer border and intercepting T cells there.

Current Alzheimer’s drugs lecanemab and donanemab target amyloid plaques and slow cognitive decline, but haven’t been shown to stop neurons from dying. Senior author David Holtzman noted plainly that in tauopathies, including Alzheimer’s disease, no treatment today actually decreases neurodegeneration. Because the antibody worked without entering the brain, Holtzman suggested a therapy along these lines might not need to be engineered to cross the blood-brain barrier at all — a significant practical advantage, since several T-cell-targeting drugs already approved for multiple sclerosis and other autoimmune conditions could potentially be repurposed and tested for Alzheimer’s. More research is needed before any human trials begin.

Journal: Neuron
Article Title: Peripheral CXCR3 blockade mitigates T cell infiltration and neurodegeneration in a mouse model of tauopathy
DOI: 10.1016/j.neuron.2026.08.030
Publication Date: September 28, 2026

Source: EurekAlert