A specific gene may protect against the development of a particular kind of dementia, according to a new study.
People who have frontotemporal lobar degeneration, or FTLD, experience a loss of brain volume in a region at the front and sides of the brain known as the frontal temporal lobe. This type of dementia can lead to speech, language and behavioral problems as well as trouble thinking and reasoning, according to the Mayo Clinic.
It was assumed that people with a mutation in the gene for the progranulin protein a protein that supports brain neurons had a high risk of developing FTLD. But the new study shows a particular version of a gene called TMEM106B may cancel out the first mutation's harmful effects.
"This was an unexpected but very exciting finding, because it suggests that if we could understand what TMEM106B is, and how it and its variants work, this could provide a new avenue for development of an agent that protects against FTLD," said study researcher Rosa Rademakers, a neuroscientist at the Mayo Clinic's campus in Florida.
Rademakers and her colleagues examined the genomes of 82 FTLD patients who had progranulin mutations, 562 FTLD patients without mutations, and 822 healthy people without FTLD.
The researchers found that individuals with a mutation but who also had inherited two copies of the protective TMEM106B gene did not develop FTLD or developed it at a much later age than is typical, which is normally around age 60, Rademakers said. (Humans inherit one copy of the gene from each parent).
"Since progranulin mutation carriers produce 50 percent less progranulin protein, we believe TMEM106B may affect progranulin levels and therefore specifically works in people with progranulin mutations," she said.
In support of their hypothesis, the researchers found that individuals carrying the protective TMEM106B allele have more progranulin in their blood plasma. That suggests the protective allele works to increase progranulin protein levels.
"The protective form of TMEM106B leads to higher levels of progranulin in the blood. Whether it also increases the levels of progranulin in the brain has not yet been studied and will be the focus of our future research," Rademakers said.
The beneficial TMEM106B gene not only could be the basis of a novel therapy for individuals with a progranulin mutation, it might help others who are at risk for dementia , she added.
The study was funded by the National Institutes of Health and the Consortium for Frontotemporal Dementia Research.
