'Supportive' brain cells may actively drive cognitive decline

Research reveals that brain cells responsible for producing the protective myelin coating around nerve fibers may actively contribute to cognitive decline as people age. A study published in Nature Medicine found that individuals with more severe cognitive decline exhibited alterations in nerve fibers and myelin compared to those with milder decline.

Experiments on mice demonstrated that disrupting oligodendrocytes, the cells that produce myelin, also impacted the coating and cognitive performance. This discovery, which contradicts the previous belief that these cells are always supportive, may lead to novel treatments targeting oligodendrocyte dysfunction to preserve cognition in later life.

The research was based on brain tissue analysis from the Lothian Birth Cohort 1936, a group of individuals assessed for cognitive abilities from childhood into older age, with follow-up cognitive testing conducted for 866 participants after age 70. Further analysis of postmortem brain tissue revealed that severe cognitive decline was linked to fewer large nerve fibers, excess unhealthy myelin, and reduced levels of the NRF2 protein in oligodendrocytes.

NRF2 regulates numerous genes involved in cell protection and healthy function. Mice experiments showed that reduced NRF2 activity in oligodendrocytes led to excess myelin, fewer large nerve fibers, and impaired cognitive performance. The findings suggest that NRF2 activity reduction can drive oligodendrocyte dysfunction, contributing to cognitive decline associated with aging.

The NRF2 pathway is already targeted by drugs, including one used to treat multiple sclerosis, suggesting potential repurposing for cognitive decline treatments.