Researchers at Washington University School of Medicine in St. Louis report that the immune cells implicated in Alzheimer's-related brain damage may be getting their marching orders from outside the brain entirely. Working in mice, the team found that T cells receive signals from lymph nodes that appear to prime them to enter the brain and contribute to neurodegeneration. When the researchers interrupted those signals, the degeneration was dramatically reduced.
T cells - the immune cells that normally hunt down infected or foreign cells - show up in unusually large numbers in the brains of people with Alzheimer's disease and related disorders, and evidence has pointed to them as active participants in the damage rather than bystanders. What has been missing is an account of where those cells come from and what sends them there. The lymph node signal identified in this work offers a candidate answer.
The study focused on conditions marked by tangled accumulations of tau protein, including Alzheimer's and the primary tauopathies. David M. Holtzman, MD, the Barbara Burton and Reuben M. Morriss III Distinguished Professor in WashU Medicine's Department of Neurology and senior author of the study, said the most intriguing aspect is that the process starts outside the brain. That matters practically: the peripheral immune system is generally easier to reach with drugs, and better characterized, than the tightly guarded environment behind the blood-brain barrier.
For now this is a mouse finding, and the path from an interrupted immune signal in an animal model to a therapy that slows tau-driven damage in people is a long one. What it adds is a new place to look - a pathway that was not previously on the map for researchers trying to slow neurodegeneration.