A few years ago, scientists saw something surprising in the brain tissue of people who died with Alzheimer’s disease: white blood cells that multiply in response to foreign threats and are seldom seen inside healthy brains.
Whether these so-called CD8+ killer T cells, which normally target infected cells in the body, were there to harm or help was unclear. An answer began to emerge in 2023, when a team led by neuroscientist David Holtzman showed that in mice bred to overexpress tau—a toxic protein that builds up in the neurons of people with Alzheimer’s and several other neurodegenerative diseases—getting rid of the T cells stemmed tissue loss and preserved the mice’s cognition, even as tau kept building up.
Now, the same group has explored what prompts these cells to wreak havoc in the brain. In a mouse study published last week in Nature Neuroscience, Holtzman and immunology researcher Hao Hu, both at Washington University in St. Louis, report that immune cells in the lymph nodes of the neck instruct the T cells to clone themselves before they enter the brain. Without them, the mice had far fewer cloned T cells inside their brains and experienced less neurodegeneration. The study is “beautiful work,” says neuroscientist Kenneth Kosik of the University of California, Santa Barbara, who studies tau but was not involved in the research. It also suggests that existing drugs, developed for other conditions, might work in Alzheimer’s by shielding the brain from the destructive cells.
