Senescent brain immune cells secrete protein linked to cognitive decline

Brain-resident immune cells that have reached an old-age state called "senescence" secrete a protein that causes dysfunction in other brain cells, according to a study led by investigators at Weill Cornell Medicine. The discovery sheds light on how aging impairs memory and cognition and makes the brain vulnerable to neurodegenerative disorders.

The researchers, whose findings are published Aug. 11 in Neuron, observed that in a mouse model of accelerated aging, many immune cells in the brain enter a non-dividing, dysfunctional, senescent state and begin secreting a protein called DLK1. This protein disrupts other brain cells, in particular neurons and the oligodendrocytes that help protect nerve fibers. The findings suggest that DLK1-driven dysfunction may be a key mechanism through which aging brings reduced brain functioning and increased neurodegenerative disease risk.

One strategy we hope to test is to neutralize this secreted protein in the brain to see if that effectively slows brain aging."

Dr. Li Gan, study lead author, the Burton P. and Judith B. Resnick Distinguished Professor in Neurodegenerative Diseases and director of the Helen and Robert Appel Alzheimer's Disease Research Institute, Weill Cornell Medicine