UVA Study Offers New Clue to How the Brain Contains Alzheimer’s Plaques
In mice, a gene called CASS4 helped the brain’s immune cells surround and pack down plaques linked to Alzheimer’s disease.
CHARLOTTESVILLE, VA — Researchers at the University of Virginia have found a new clue to how the brain defends itself against one of the hallmarks of Alzheimer’s disease. In a mouse study, a gene called CASS4 helped the brain’s immune cells gather around plaques and pack them more tightly, a response that can help protect nearby nerve cells.
Previous studies had linked CASS4 to Alzheimer’s risk in people, but how the gene might influence the disease was unclear. The UVA team looked at microglia, immune cells that live in the brain. These cells can form a barrier around plaques, which are clusters of a protein fragment called amyloid beta.
When the researchers removed CASS4 in mice bred to develop amyloid plaques, fewer microglia gathered around the deposits. The plaques were less tightly packed, amyloid buildup increased, and nerve fibers near the plaques showed more damage. Removing the gene specifically from microglia produced similar changes.
Adeline “Addie” Walsh, a UVA physiology graduate student, was the study’s first author. John Lukens, who directs UVA’s Harrison Family Translational Research Center in Alzheimer’s and Neurodegenerative Diseases, led the team. UVA Health announced the findings Nov. 10.
The results give researchers a specific question to pursue. Could boosting CASS4 activity help the brain’s immune cells contain plaques? The team studied what happened when the gene was removed in mice. Whether increasing its activity could slow Alzheimer’s in people remains an open question.
Read the study in the Journal of Experimental Medicine.
