Jessica Rexach, MD, PhD and Mai Yamakawa, MD: UCLA neurologists find elevated levels of specific immune cell in Alzheimer’s disease patients

Mai Yamakawa, MD

"When Mai Yamakawa, MD, downloaded single-cell genetic profiles from brains affected by Alzheimer’s disease, she and her colleagues began an intense search for a specific immune cell: the T lymphocyte.

Previous research on mouse models and human spinal fluid hinted that they would find it. But parsing through data from human brain tissue required much more sophisticated and time-intensive analysis.

Nearly a year later, they found that of the 1.2 million cells in the dataset, a mere 800 were T cells, with the CD8 subclass most abundant. These effector memory cells contribute to inflammation by killing target cells and modulating the immune response.

“It’s a needle in a haystack but we proved that it's there,” said Dr. Yamakawa, a clinical instructor in neurology at the David Geffen School of Medicine at UCLA. “The immune system is one of the most diverse systems between individuals. But we were able to capture a signature [of the disease] from 70 different people.”

jessica rexach

Dr. Yamakawa and principal investigator Jessica Rexach, MD, PhD, showed for the first time that CD8 T cells were consistently elevated in human brains with Alzheimer’s disease, as well as characterizing some of their interactions with microglia, the brain’s resident immune cells.

The findings further refine the molecular landscape of Alzheimer’s disease and point to the important role of neuroinflammation in disease progression.

Their study “Cell States and Interactions of CD8 T Cells and Disease-Enriched Microglia in Human Brains with Alzheimer’s Disease” was published in the journal Biomedicines in January.

“[CD8 T] cells are not a very abundant cell type in the brain, but they're one of considerable interest,” said Dr. Rexach, an assistant professor in neurology and the division of neurogenetics at DGSOM. “When you look at the animal model work, there's actually a bit of controversy about whether these cells are providing a beneficial role [or] whether they're providing a deleterious role.”

For example, a study last year examined intercellular communication between microglia and CD8 T cells, and found that the T cells protected mouse brains from neuroinflammation and cognitive decline."

Read more at UCLA Health.