Discovery of T cells' role in Alzheimer's, related diseases, suggests new treatment strategy

Studying mice with Alzheimer’s-like damage in their brains due to the protein tau, the researchers discovered that microglia attract powerful cell-killing T cells into the brain, and that most of the neurodegeneration could be avoided by blocking the T cells’ entry or activation. The findings, published in the journal Nature, suggest that targeting T cells is an alternative route to preventing neurodegeneration and treating Alzheimer’s disease and related diseases involving tau, collectively known as tauopathies.

The researchers found many more T cells in the brains of tau mice than the brains of amyloid or comparison mice. Notably, T cells were most plentiful in the parts of the brain with the most degeneration and the highest concentration of microglia. T cells were similarly abundant at sites of tau aggregation and neurodegeneration in the brains of people who had died with Alzheimer’s disease.

Eliminating either microglia or T cells broke the toxic connection between the two and dramatically reduced damage to the brain. For example, when tau mice were given an antibody to deplete their T cells, they had fewer inflammatory microglia in their brains, less neurodegeneration and atrophy, and an improved ability to perform tasks such as building a nest and remembering recent things.

Reference:

Discovery of T cells’ role in Alzheimer’s, related diseases, suggests new treatment strategy; Nature; DOI: 10.1038/s41586-023-05788-0