A genetic variant in some people may be associated with mental decline that can't be explained by deposits of two proteins linked with Alzheimer's disease, researchers say.
They said their findings could lead to new treatments for Alzheimer's.
The two proteins are amyloid β and tau. Amyloid forms into plaques and tau forms into tangles. Both are found in the brains of Alzheimer's patients, but can also occur in the brains of older people who don't have memory or thinking problems.
In this study, researchers discovered a gene variant on the sixth chromosome that alters the metabolism of an antioxidant called glutathione. It may be associated with thinning of the brain's cortex, which plays a role in memory and thinking skills.
The findings were published online Sept. 16 in the journal Neurology.
"Our study identified one significant single nucleotide polymorphism related to cognitive [mental] decline independent of amyloid β and tau protein deposits in the brain," study author Dr. Yong Jeong said in a journal news release.
"We showed that this genetic variation negatively affects thinking and memory skills, partly because it's associated with thinning in the cortex of the brain," he added.
Jeong is an assistant professor in the Department of Bio and Brain Engineering at the Korea Advanced Institute of Science and Technology in Daejeon, South Korea.
The study included 486 people who all had amyloid β deposits in the brain. Some had normal thinking and memory skills, some had mild mental impairment, and some had Alzheimer's.
The researchers used genetic analysis to identify gene variants associated with mental function independent of amyloid and tau. They estimated that 5% of the variance in mental function was explained by the single gene variant.
Even though people with the variant had similar amounts of amyloid β and tau protein deposits in their brains as those without the gene variant, they had lower scores on tests of thinking skills.
Among those with the gene variant, 11% had normal thinking skills, compared to 25% of those without the variant. Mild impairment was found in 40% of those with the variant and in 46% of those without it. And 49% of those with the variant had Alzheimer's, compared to 29% of those without the variant.
"Deposits of amyloid β and tau proteins in the brain may be required for a diagnosis of Alzheimer's disease, but the current thinking is that they are not by themselves enough to cause cognitive decline and dementia," Jeong said. "Understanding the genetic mechanisms underlying the development of Alzheimer's may lead to the development of new treatments for this devastating disease."