Julia Belk was trained in computer science before she ever touched a microscope. Now she is publishing discoveries in Nature that could change how scientists understand the aging brain.
Belk, a postdoctoral scholar at Stanford Medicine, is the first author of a new study that found large numbers of immune cells from the bloodstream regularly enter the human brain as people age. For decades, most researchers believed the brain's immune system worked independently, sealed behind a protective barrier that kept out foreign cells. This new research challenges that assumption entirely.
"What we found is that actually a lot of immune cells enter the human brain during aging," Belk said.
The discovery began with an earlier observation. Belk collaborated with Siddhartha Jaiswal, an associate professor of pathology at Stanford Medicine and senior author of the new study. Their earlier work examined genetic information from thousands of people followed over decades. They discovered that people carrying certain clones of immune cells produced by mutated blood stem cells were much less likely to develop Alzheimer's disease. This surprising result suggested these unusual immune cells might somehow interact with the brain.
The team later found evidence that some of these mutant cells could cross into the brain itself. That led to a bigger question: If mutant cells could enter in some people, could ordinary immune cells from the blood regularly enter the brains of everyone as they grow older?
To find out, the researchers studied brain tissue from the Stanford Rapid Autopsy Center, led by professor Jody Hooper, along with samples from the University of Washington's Alzheimer's Disease Sequencing Project. These programs collect both blood and post-mortem brain tissue, giving scientists a rare chance to compare immune cells in the bloodstream with those found in brain tissue after death.
The team used genetic tracing methods to determine where brain immune cells originated. They found that many cells presumed to be permanent brain residents actually came from the bloodstream. The findings suggest the brain's immune population is not self-sustaining as scientists long believed. Instead, it receives ongoing reinforcements from the rest of the body.
Howard Chang, a professor of genetics at Stanford Medicine and co-senior author, helped lead the investigation with support from the Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute. The initiative funds research meant to rethink how scientists study brain aging and neurodegenerative disease.
The implications extend beyond basic science. If immune cells regularly enter the aging brain, they might play a role in either protecting against or contributing to diseases like Alzheimer's. That could eventually open new doors for treatment.
"This opens up a whole new area of investigation," Jaiswal said.