Brain imaging and gene analyses in twins reveal that white matter integrity is linked to an iron homeostasis gene.
Iron deficiency is a well-known cause of impaired cognitive, language, and motor development, but a report out today (January 9) in Proceedings of the National Academy of Sciences reveals that even in apparently healthy young adults, variations in iron levels correlate with variations in brain structure integrity.
“[The researchers] make a very interesting connection between the issue of iron metabolism and the integrity of white matter, more specifically myelin”—the cellular sheath that enwraps and insulates neuronal axons—said George Bartzokis of the University of California, Los Angeles, who was not involved in the study. “This would have been predicted by what is known about myelin, because it actually contains a lot of iron, so it is important that [they have] directly demonstrated this in humans with imaging.”
Children that are iron deficient—often as a result of poor diet—score poorly in mathematics and language tests. Given such effects, Paul Thompson of the UCLA and his colleagues decided to “look to see if, even among normal healthy kids, variations in their iron levels that are fairly subtle end up mattering. And the surprise is, they matter a lot.”
The team measured blood serum transferrin levels—an inverse but more reliable measure of available iron—in adolescents, and then performed brain scans when these teens reached their early twenties. Among other things, the team looked at myelin function using a technique called diffusion tensor imaging, and found a strong positive correlation between teen iron levels and myelin integrity in the twenty-something subjects.
“We’re very surprised at how much of a difference it makes to your brain to have good iron in your diet when you’re developing,” said Thompson. “The simplest message is that the iron in your diet as a teenager is associated with better brain integrity when you grow up.”
Thompson and colleagues also investigated whether there was a genetic contribution to iron availability and brain structure. Of the study subjects, which were either identical or non-identical twins, the link between iron levels and myelin integrity between twins was stronger if they were identical. That is, high iron levels in one twin could better predict myelin integrity in the other.
Further investigation of two iron homeostasis genes revealed that a polymorphism in one—HFE, which regulates cellular absorption of transferrin-bound iron—was associated with both high iron levels and improved white matter integrity.
Of course having this polymorphism does not automatically mean better brain function. The current study has not investigated such a link with the polymorphism, or indeed with serum transferrin or white matter integrity—something that would be important to show, said James Connor of Penn State University. “You want to see whether these differences matter in terms of their cognitive skills.”
And even if the HFE variant did improve brain function, there is a risk that the same polymorphism might pose a problem in older adults. Iron accumulation in the brain has been suggested to be a contributing factor to a number of neurodegenerative disorders, explained Thompson. “So it’s a double-edged sword.”
One thing is certain, said Connor: given the prevalence of this polymorphism—which is carried by about 12-15 percent of Caucasians—whichever way the results shake out, “these data are going to be relevant to a large percentage to the population.”