Immune cells from the neck cause Alzheimer’s in the brain

In a strange reflection of the last post here, Science has a report on a study at Washington University in St. Louis that’s found immune cells produced by lymph nodes in the neck can cause the cell damage in the brain responsible for Alzheimer’s and related degenerative diseases:

The new study homes in on a type of dendritic cells, immune cells that, in effect, give the killer T cells their orders. After cutting up the invader’s proteins, the dendritic cells present the antigens as bite-size pieces that T cells can recognize. T cells with compatible receptors can then become activated, which causes the cells to start to clone themselves, attack cells bearing the antigen, and cause inflammation.

[David] Holtzman and [Hao] Hu studied the role of dendritic cells by ensuring that half of their tau-overexpressing mice were genetically incapable of making them. The researchers then observed mice from both groups—some 80 animals in all—through about 10 months of age, when they normally have brain damage and severe behavioral symptoms, including trouble building nests. Both groups continued to accumulate tau, but those lacking the dendritic cells were largely protected from neurodegeneration and behavioral problems.

The finding suggests tau, suspected of killing neurons in Alzheimer’s and other neurodegenerative diseases, does not act alone. Tau probably leads to some injury, Holtzman thinks, “but the inflammation is really amplifying the injury. It’s an important issue [to consider] in developing future therapies.”

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The finding that this process occurs in the neck, not the brain, is crucial, says neuroimmunology researcher John Lukens of the University of Virginia. That’s because it suggests tamping down the number of destructive T cells in the brain would not require a drug to cross the blood-brain barrier—a persistent challenge in developing drugs for neurodegenerative disease.

Better yet, existing drugs may be able to help. Several treatments for multiple sclerosis work by trapping T cells in the lymph nodes, away from the brain and spinal cord. In theory, Lukens says, these drugs “could be rapidly co-opted for the treatment of tauopathies and Alzheimer’s disease.” The next step “would be to uncover the specific [signaling proteins] that orchestrate T cell recruitment to the brain in tau-driven neurodegenerative diseases.”

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You can read more of the T-cell brain research here, in Nature Neuroscience.