T Cells May Play a Role in the Brain Inflammation Characteristic of Neurodegenerative Conditions
Alzheimer's disease, and other forms of neurodegenerative condition, are characterized by chronic inflammation in brain tissue. Unresolved inflammatory signaling is disruptive of tissue structure and function. Here, researchers provide evidence for T cells to become involved in this process. Normally T cells of the adaptive immune system do not enter the brain in any great numbers, but those numbers are greater in Alzheimer's patients. Researchers here show that eliminating these T cells slows the progression of neurodegeneration in animal models, suggesting that this approach may be worth trying in human clinical trials.
Many of the immunity-focused Alzheimer's drugs under development are aimed at microglia, the brain's resident immune cells, which can injure brain tissue if they're activated at the wrong time or in the wrong way. A new study indicates that microglia partner with another type of immune cell - T cells - to cause neurodegeneration. 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 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.
"This could really change the way we think about developing treatments for Alzheimer's disease and related conditions. Before this study, we knew that T cells were increased in the brains of people with Alzheimer's disease and other tauopathies, but we didn't know for sure that they caused neurodegeneration. These findings open up exciting new therapeutic approaches. Some widely used drugs target T cells. Fingolomid, for example, is commonly used to treat multiple sclerosis, which is an autoimmune disease of the brain and spinal cord. It's likely that some drugs that act on T cells could be moved into clinical trials for Alzheimer's disease and other tauopathies if these drugs are protective in animal models."