A single stroke doubles a person’s risk of developing dementia over the following decade, even when that person’s mental ability is initially unaffected. Why this delayed deterioration occurs has been a mystery. Now, Stanford University School of Medicine investigators think they have discovered a major reason for it.
In experiments using both mouse models of stroke and brain-tissue samples from humans, they linked the delayed onset of post-stroke dementia to the persistent presence, in the brain, of specialized immune cells that shouldn’t be there at all.
The discovery could potentially translate into ways of identifying people at risk for dementia, allowing physicians time to try to stave off the disease. Drugs that can disable these immune cells are already available.
At roughly 800,000 new cases per year, stroke is the second-biggest cause of serious long-term disability in the United States, generating $74 billion annually in treatment and caretaking costs. Of the 7 million living stroke survivors nationwide, one-third either suffers from dementia, or will.
In a study to be published in The Journal of Neuroscience, a team directed by Marion Buckwalter, MD, PhD, assistant professor of neurosurgery and of neurology and neurosciences, examined several mouse models of stroke, as well as human brain-tissue samples, and found strong evidence that antibody-producing cells called B cells play a key role in the delayed onset of dementia. Buckwalter is the study’s senior author. The lead author is former postdoctoral scholar Kristian Doyle, PhD.
B cells help, usually
The antibodies that B cells produce are normally of great value to us. They circulate throughout blood and lymph, and bind to microbial invaders, gumming up the pathogens’ nefarious schemes and marking them for destruction by other immune cells. Occasionally, B cells wrongly begin generating antibodies that bind to the body’s own healthy tissues, causing certain forms of autoimmune disease, such as rheumatoid arthritis. Rituxan, a drug approved by the Food and Drug Administration for this condition, is actually an antibody itself: Its target is a protein found on the surface of every B cell. Use of this drug depletes B cells in the body, relieving the symptoms of rheumatoid arthritis and other B-cell-mediated disorders.
Like almost all other types of immune cells, B cells are virtually nonexistent in the brains of healthy people, whose outermost ramparts are mostly impervious to the cells and large molecules (like antibodies) freely circulating elsewhere. But the blood-brain barrier is not entirely unbreachable and is rendered much more permeable upon brain damage.
The study was supported by the National Institutes of Health (grants R01NS067132 and K99NR012593). Other Stanford co-authors are neurology professor Lawrence Steinman, MD; Frank Longo, MD, PhD, professor and chair of neurology; visiting scholar Montse Sole, PhD; research associate Thuy-Vi Nguyen, PhD; postdoctoral scholars Robert Axtell, PhD, Gilberto Soler-Llavia, PhD, and Sandra Jurado, PhD; and life science research assistants Jullet Han and Lisa Quach.