Researchers at Washington University School of Medicine in St. Louis have identified a potential new approach to protecting brain cells from damage associated with Alzheimer’s disease and other tauopathies.

In a study involving mice with Alzheimer’s-like tau accumulation, researchers blocked a pathway used by immune cells called T cells to enter the brain. The treatment involved an antibody targeting a protein called CXCR3 and was administered through injections outside the brain.

The researchers found that blocking CXCR3 reduced the number of T cells entering the brain by approximately half. Despite no change in the amount of tau accumulation, treated mice preserved about 40% more tissue in brain regions involved in memory and performed better on memory tests than untreated mice.

The findings, published Sept. 28 in Neuron, build on earlier research showing that T cells may contribute to brain damage in tauopathies. Previous studies from the same research group found that T cells accumulate in areas of the brain where tau levels are high and may contribute to neurodegeneration.

The new study focused on understanding how these immune cells enter the brain. Researchers identified the interaction between the chemokine CXCL10 and its receptor CXCR3 as an important pathway. When either CXCL10 or CXCR3 was absent, T cells were largely prevented from entering the brains of mice, even when inflammation was deliberately triggered.

The team then treated young mice with tau accumulation using an antibody that blocked CXCR3 every five days for three and a half months. At the end of the treatment period, the mice had approximately half as many T cells in their brains, greater preservation of brain tissue, and fewer signs of nerve-cell damage compared with untreated animals.

Importantly, the antibody reached the border of the brain without entering the brain tissue itself. This suggests that targeting immune activity outside the brain could potentially protect against neurodegeneration without requiring a drug to cross the blood-brain barrier.

The findings point to a potential therapeutic strategy that focuses on the immune response to tau rather than directly removing tau itself. Existing therapies that target T cells and are used for conditions such as multiple sclerosis and other autoimmune diseases could potentially be investigated for their relevance to tau-related neurodegenerative diseases.

However, the research is currently limited to an animal model, and further studies are needed to determine whether this approach is safe and effective in people with Alzheimer’s disease or other tauopathies.

Source: https://medicine.washu.edu/news/blocking-immune-cells-path-into-brain-limits-neurodegeneration/