Summary of Blocking T Cells To Prevent Neurodegeneration:
Researchers at Washington University School of Medicine in St. Louis have discovered that microglia, the brain’s resident immune cells, partner with T cells to cause neurodegeneration in Alzheimer’s disease and related diseases involving the protein tau. By blocking T cells’ entry or activation, researchers were able to prevent most of the neurodegeneration in mice with Alzheimer’s-like brain damage. These findings suggest that targeting T cells could be an effective way to prevent neurodegeneration and treat these diseases. Many experimental therapies targeting the immune system are already in clinical trials for Alzheimer’s disease.
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Brain Damage in Alzheimer’s Linked to T Cells, Study Finds
A new study from researchers at Washington University School of Medicine in St. Louis suggests that a type of immune cell – T cells – are responsible for the neurodegeneration seen in Alzheimer’s disease and related tauopathies. The research found that microglia, the brain’s resident immune cells, partner with T cells to cause neurodegeneration. By blocking the entry or activation of T cells, the researchers were able to prevent most of the neurodegeneration in mice with Alzheimer’s-like brain damage caused by the tau protein.
The findings, published in the journal Nature, challenge the current focus on targeting microglia for treating Alzheimer’s and related diseases. Nearly two dozen experimental therapies targeting the immune system are in clinical trials for Alzheimer’s disease, but most of them target microglia. These drugs could injure brain tissue if they’re activated at the wrong time or in the wrong way.
Alzheimer’s disease affects memory, thinking, and behavior and is the most common cause of dementia. The disease is characterized by the abnormal accumulation of proteins in the brain, which form plaques and tangles that damage and kill brain cells. There is currently no cure for Alzheimer’s disease, but medications and lifestyle interventions can help manage symptoms and slow the progression of the disease.
“These findings open up exciting new therapeutic approaches,” said senior author David M. Holtzman, MD. “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.”
The study’s first author, Xiaoying Chen, PhD, wondered about the role of other, less studied immune cells in neurodegeneration. She analyzed immune cells in the brains of mice genetically engineered to mimic different aspects of Alzheimer’s disease in people, looking for changes to the immune cell population that occur over the course of the disease.
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. Eliminating either microglia or T cells broke the toxic connection between the two and dramatically reduced damage to the brain.
“What got me very excited was the fact that if you prevent T cells from getting into the brain, it blocks the majority of the neurodegeneration,” Holtzman said. “Scientists have put a lot of effort into finding therapies that prevent neurodegeneration by affecting tau or microglia. This highlights a new area to better understand and therapeutically explore.”
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