Scientists have discovered evidence that some of the immune activity linked to Alzheimer’s-like brain damage may start outside the brain, opening a potential new avenue for future treatments. In a study in mice, published in Nature Neuroscience, researchers found that immune cells known as T cells, which have been associated with brain damage in Alzheimer’s disease and related disorders, appear to be receiving instructions from lymph nodes rather than from inside the brain itself. The process involves another type of immune cell called dendritic cells.
The finding could be significant because researchers have long known that T cells accumulate in the brains of people with Alzheimer’s disease and related conditions. These cells are believed to contribute to damage in the brain, but scientists have not fully understood where they come from or what drives them to gather there. To investigate, researchers studied mice that develop tau tangles, abnormal twisted clumps of tau protein that are a hallmark of Alzheimer’s disease and other conditions known as primary tauopathies.
The team found little evidence that a specific type of dendritic cell, known as classical dendritic cells type 1 (cDC1), was directing T cell activity from within the brain. There were very few of these dendritic cells present in the brain, and those that were there did not appear to interact with the T cells that accumulated after tau tangles developed. The results led researchers to suspect that both dendritic cells and T cells were being activated elsewhere in the body.
To test the idea, the scientists removed dendritic cells from lymph nodes and other locations in mice that would normally develop tau tangles and neurodegeneration. The effects were striking. The unusually high numbers of T cells found in the brain disappeared, and levels of CD8 T cells were significantly reduced.
At the same time, brain damage associated with neurodegeneration was greatly reduced. Perhaps most notably, the amount of tau tangles in the brain remained unchanged. In other words, even though the protein clumps thought to drive disease were still present, the damage to the brain was reduced when the immune pathway involving dendritic cells and T cells was blocked.
The mice also maintained their cognitive abilities, suggesting that limiting T cell activity could help slow or reduce cognitive decline associated with Alzheimer’s disease. Researchers do not yet know exactly what activates the dendritic cells. However, they believe the most likely explanation begins with tau-related damage to brain cells.
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