Oligodendrocyte dysfunction linked to age-related cognitive decline

Research published in Nature Medicine suggests that dysfunction in oligodendrocytes—the brain cells responsible for producing myelin—may drive age-related cognitive decline in humans.

By analyzing data from the Lothian Birth Cohort 1936, which included lifelong cognitive tracking and postmortem brain analysis, researchers observed that individuals experiencing greater cognitive decline exhibited smaller myelinated axons paired with thicker myelin sheaths.

To investigate the underlying mechanisms, researchers conducted mouse experiments. They found that deleting the gene encoding nuclear factor erythroid 2-related factor 2 (NRF2) from oligodendrocytes in mice produced alterations in axon size and myelin thickness similar to those seen in humans, alongside reduced cognitive improvement over time. These findings suggest that oligodendrocyte density, reduced NRF2 expression, and damage to myelinated axons are key cellular changes linked to cognitive impairment.