A clue as to how some people develop a form of dementia that affects the brain areas associated with personality, behavior, and language has been discovered by scientists.
Researchers at the Mayo Clinic campus in Florida said they found a link between two proteins - progranulin and sortilin - which might open new avenues for the treatment of frontotemporal lobar degeneration (FTLD), which occurs in the frontal lobe and temporal lobe of the brain.
This form of dementia, which is currently untreatable, generally occurs in younger people, compared to other common neurodegenerative disorders such as Alzheimer's disease.
"We now can look for a direct link between these two proteins and the development of FTLD," said the study's lead author, neuroscientist Rosa Rademakers.
"The hope is that if we do find a strong association, it might be possible to manipulate levels of one or both of these proteins therapeutically," the author said.
Based on their previous findings that a simple blood test is able to measure progranulin levels in plasma and could be used to identify patients with progranulin mutations, they tested blood from 518 healthy individuals in a GWAS to look for genetic variants that could explain some of the normal variability of progranulin levels in plasma.
They found very strong association with two genetic variants in the same region of chromosome 1 and confirmed this finding in a second group of 495 healthy individuals.
By reviewing the scientific literature, they further ascertained that the same genetic variant found to be associated with plasma progranulin levels also affects the levels of the protein sortilin.
Like progranulin, sortilin is found throughout the body and is involved in different tasks. In the brain, it is known to be important for survival of brain neurons.
The researchers then studied the two proteins in cell culture and showed that the amount of sortilin in cells determines how much progranulin is taken inside or remains outside of a cell.
The study was published in the Nov. 17 online issue of the American Journal of Human Genetics.