Losing the Frem3 gene lowers brain volume in aging mice

In an animal experiment, researchers studied mice engineered to lack the Frem3 gene specifically in excitatory neurons, brain cells that stimulate other nerves. The team evaluated the animals in young adulthood and middle age. Mice lacking Frem3 showed widespread lower global and regional brain volume in middle age compared with young adulthood, a pattern of loss absent in normal mice. These reductions were strongest in cortical regions tied to cognition and were accompanied by lower cognitive performance. In humans, the researchers conducted an observational study using genetically predicted activity of the FREM3 gene. Lower estimated FREM3 activity was associated with lower total brain surface area. That lower surface area mediated an indirect link to lower cognitive performance across multiple age-sensitive domains.