Immune cells outside brain may drive Alzheimer’s-related neurodegeneration

Researchers used mice to investigate how T cells contribute to brain cell destruction in Alzheimer’s disease and related disorders.(CN) — Researchers posit that the brain damage associated with Alzheimer’s and similar neurological diseases may actually start outside of the brain.Immune cells called T cells accumulate in the brain with Alzheimer’s-related tau buildup and contribute to brain damage. But researchers in a study published Thursday in Nature Neuroscience theorize the cells may be activated elsewhere in the body, suggesting a potential way to slow neurodegeneration without directly targeting the brain.Using mice as test cases, they found that eliminating a type of immune cell called a classical dendritic cell, or cDC1, from mice genetically prone to tau-related disease sharply reduced the number of T cells in their brains and protected against neurodegeneration.The mice still developed tau tangles but experienced less brain damage and retained their cognitive abilities, according to the researchers from Washington University School of Medicine in St. Louis.The findings suggest that tau accumulation and the immune response that causes subsequent brain damage may be separate processes, said David Holtzman, a professor of neurology at Washington University and senior author of the study.“One of the issues in developing treatments for neurological diseases is that you need to engineer your treatment so that it gets into the brain and past the blood-brain barrier,” Holtzman said in a press release. “But we might not actually need to get the drugs into the central nervous system to mitigate neurodegeneration.”Holtzman’s laboratory previously found that removing T cells from mice prevented much of the brain damage associated with tau buildup. The new study sought to determine where those T cells were being activated.The researchers found very few cDC1 cells in the brains of mice with tau pathology, leading them to look at tissues outside the brain.When cDC1 cells were eliminated from lymph nodes and other peripheral tissues, the mice had substantially fewer T cells in their brains, particularly CD8 T cells, which can destroy targeted cells. The reduction was accompanied by less neurodegeneration despite continued tau buildup.Researchers suspect that damage caused by tau may cause brain cells to release material that drains into lymph nodes in the neck. There, dendritic cells could activate T cells, which then migrate toward the brain and contribute to further damage.The study does not establish that the same process occurs in people with Alzheimer’s disease. But Holtzman said existing treatments that manipulate T cells could make the peripheral immune system a potential target for future research.Categories / Health, ScienceSubscribe to our free newslettersOur weekly newsletter Closing Arguments offers the latest about ongoing trials, major litigation and rulings in courthouses around the U.S. and the world, while the monthly Under the Lights dishes the legal dirt from Hollywood, sports, Big Tech and the arts.Additional Reads