Brain cells that normally shield nerve fibers may actually contribute to memory loss and thinking difficulties as people age, according to a new study published in Nature Medicine. Scientists from the University of Edinburgh and the UK Dementia Research Institute discovered that these cells, known as oligodendrocytes, can become dysfunctional over time, potentially accelerating cognitive decline.
The findings challenge the long-held assumption that oligodendrocytes are always beneficial. While these cells produce myelin, the protective coating that allows electrical signals to travel efficiently through the brain, the research indicates that excessive or abnormal myelin buildup can damage nerve fibers and interfere with brain function.
Lothian Birth Cohort Findings
The study analyzed data from the Lothian Birth Cohort 1936, a group of individuals whose cognitive abilities have been tracked from childhood into old age. Of the 1,091 participants, 866 completed additional cognitive testing after age 70. Assessments measured memory, processing speed, and spatial understanding between ages 70 and 82.
Nearly all participants experienced some degree of cognitive decline, but the rate varied significantly. Researchers examined brain tissue collected after death from a subset of these individuals and identified a clear pattern. Those with the most severe cognitive decline had fewer large nerve fibers and an abnormal accumulation of unhealthy myelin.
These abnormalities were particularly noticeable around the remaining large nerve fibers. Importantly, the changes correlated with the speed of cognitive deterioration rather than baseline performance at a specific age.
The Role of NRF2 and Oligodendrocytes
To understand the cause of these changes, researchers focused on oligodendrocytes and a protein called NRF2. This protein regulates hundreds of genes involved in protecting cells from damage. The study found that individuals with severe cognitive decline had lower levels of NRF2 within their oligodendrocytes.
When NRF2 activity decreases, cells become less capable of defending themselves and performing their usual functions. To test this connection, the team conducted experiments in mice. When researchers specifically reduced NRF2 in oligodendrocytes, the animals developed excessive myelin, lost large nerve fibers, and showed reduced improvements in cognitive performance as they aged.
These results provided direct evidence that declining NRF2 activity disrupts oligodendrocyte function, triggering changes in myelin and nerve fibers that contribute to cognitive decline.
Potential for New Treatments
The discovery offers a potential new approach for protecting the aging brain. The NRF2 pathway is already a target for medications used to treat other neurological conditions. For example, a drug prescribed for multiple sclerosis has been shown to increase NRF2 activity and improve cognitive function in some patients.
This raises the possibility that existing treatments could be repurposed to address oligodendrocyte dysfunction and age-related cognitive decline. While further research is needed to determine if such treatments would benefit older adults, the findings identify a valuable therapeutic target.
Veronique Miron, a senior fellow at the University of Edinburgh and the UK Dementia Research Institute, noted the significance of the work. She stated that as the prevalence of cognitive decline rises with an aging population, this research points to a potential strategy for new therapeutic approaches to preserve cognitive ability in aging.
Georgina Craig, the study’s first author, emphasized the shift in scientific understanding. She said the study fundamentally changed how researchers view these brain cells, revealing that they can become dysfunctional and contribute to cognitive impairment in aging rather than simply providing support.
The research was funded by the UKRI Medical Research Council and the Canadian Institutes of Health Research. Additional scientists from Northwestern University and the University of Edinburgh’s Lothian Birth Cohort studies contributed to the work.
Source: ScienceDaily
