APOE4 gene variant linked to greater nerve damage in MS: Study
Carriers also showed signs of cognitive decline, more brain tissue damage
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This image shows a strand of DNA. (Photo from iStock)
- The APOE4 gene variant is linked to worse outcomes in MS patients.
- Carriers show greater nerve damage and slower cognitive processing.
- This variant may act as a genetic modifier, increasing multiple sclerosis severity.
A genetic variant strongly linked to Alzheimer’s disease may also worsen neurological damage in people with multiple sclerosis (MS), according to a new study.
Researchers found that MS patients carrying the APOE4 variant showed greater signs of neurodegeneration than those without it, including higher levels of nerve damage biomarkers, greater brain tissue damage, and slower cognitive processing.
The findings suggest “greater disease severity and worse health outcomes in MS patients who are APOE4 carriers,” researchers wrote.
The study, “Apolipoprotein E4 and its later-life health effects on the multiple sclerosis population,” was published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical.
APOE4 known to increase risk of Alzheimer’s disease
While the exact causes of MS are not fully understood, evidence suggests that a combination of genetic and environmental factors — such as viral infections, smoking, and obesity — contribute to its development and progression.
One gene that has been implicated in the genetic basis of MS is APOE, which provides instructions for making apolipoprotein E, a protein involved in transporting fats and repairing nerve cells in the brain.
A specific variant of this gene, called APOE4, is known to increase the risk of neurodegenerative diseases such as Alzheimer’s disease and has also been linked to cognitive problems in people with MS. However, how this variant affects MS progression and long-term outcomes has remained unclear.
To investigate, a group of researchers in the U.S. examined data from the U.K. Biobank, which is following hundreds of thousands of patients to understand which factors set the stage for certain diseases later in life. The team specifically assessed whether carrying the APOE4 variant influenced long-term health outcomes among people with MS.
The team focused on measures commonly used to monitor MS in the clinic. These included optical coherence tomography (OCT) scans to assess thinning of nerve fibers in the retina, which is indicative of nerve cell damage, brain MRI scans to detect structural changes, and blood tests measuring proteins linked to nerve damage and inflammation.
Participants also underwent cognitive assessments as part of the the U.K. Biobank study, and researchers used these to determine cognitive changes in people carrying the APOE4 variant.
Outcomes worse for APOE4 carriers across most measures
Of the 502,367 patients in the U.K. Biobank study, 188 MS patients who had undergone APOE genetic testing were included in the analysis. Of them, 48 carried the APOE4 variant and 140 did not.
Results showed that outcomes were worse for APOE4 carriers across most measures. Blood tests showed significantly higher levels of GFAP and NfL — markers associated with the abnormal activation of certain support cells in the brain and with nerve cell damage, respectively — compared with noncarriers. Levels of CHI3L1, a marker of inflammation, were lower in APOE4 carriers.
OCT and MRI scans showed a similar pattern, suggesting greater damage to nerve fibers connecting the eye to the brain, as well as greater brain damage, in APOE4 carriers.
Finally, cognitive testing also indicated that carriers performed more poorly on reaction-time tests than noncarriers, indicating slower cognitive processing speed.
Notably, while some effects were specific to MS, APOE4 also affected healthy individuals. In people without MS, APOE4 carriers also tended to show slower reaction times and more damage in MRI and OCT scans than noncarriers, indicating that the variant may promote neurodegeneration even in healthy people without a neurological disease.
Taken together, the findings suggest that APOE4 may act as a genetic modifier of MS, contributing to greater nerve damage and cognitive decline.
