NN: Immune cells outside the brain may damage neurons in Alzheimer’s disease

The threat posed by Alzheimer’s disease may not originate solely within the brain: immune cells activated outside the brain can trigger neuroinflammation and neuronal damage. Scientists from Washington University in St. Louis reached this conclusion in a study published in Nature Neuroscience.

Experiments in mice showed that CD8+ T cells may play a key role in this process. These immune cells normally destroy infected, abnormal, or cancerous cells. In the presence of tau pathology, they infiltrated the animals’ brains in large numbers and were associated with neurodegeneration.

The researchers found that other immune cells — cDC1, or conventional type 1 dendritic cells — may direct T cells toward the brain. These cells recognize foreign proteins and “present” them to T cells, activating an immune response.

“When cDC1 cells were removed from mice with tau pathology, signs of inflammation and neuronal damage decreased significantly. At the same time, fewer CD8+ T cells entered the brain. However, the amount of tau protein remained virtually unchanged, suggesting that brain damage may be linked not only to tau accumulation itself but also to the subsequent immune response,” the scientists explained.

The researchers hypothesized that the process begins in the brain: damaged neurons release certain protein antigens, which may then reach the deep cervical lymph nodes. There, cDC1 cells activate CD8+ T cells, after which the T cells travel back to the brain and trigger inflammation and further damage to nerve cells.

So far, the mechanism has been confirmed only in animal experiments. However, the discovery could lead to a new approach to treating neurodegenerative diseases — targeting immune cells and the lymphatic system outside the brain. This could potentially eliminate the need to cross the blood-brain barrier to deliver drugs directly into the brain.

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