Gene variant that makes brains resilient against Alzheimer`s discovered
Washington: Researchers at Vanderbilt University Medical Center have discovered a potential genetic variant in the asymptomatic individuals that may make brains more resilient against Alzheimer's.
"Most Alzheimer's research is searching for genes that predict the disease, but we're taking a different approach. We're looking for genes that predict who among those with Alzheimer's pathology will actually show clinical symptoms of the disease," principal investigator Timothy Hohman, Ph.D., a post-doctoral research fellow in the Center for Human Genetics Research and the Vanderbilt Memory and Alzheimer's Center said.
The researchers used a marker of Alzheimer's disease found in cerebrospinal fluid called phosphorylated tau. In brain cells, tau is a protein that stabilizes the highways of cellular transport in neurons. In Alzheimer's disease tau forms "tangles" that disrupt cellular messages.
Analyzing a sample of 700 subjects from the Alzheimer's Disease Neuroimaging Initiative, Hohman and colleagues looked for genetic variants that modify the relationship between phosphorylated tau and lateral ventricle dilation - a measure of disease progression visible with magnetic resonance imaging (MRI). One genetic mutation (rs4728029) was found to relate to both ventricle dilation and cognition and is a marker of neuroinflammation.
"This gene marker appears to be related to an inflammatory response in the presence of phosphorylated tau," Hohman said.
"It appears that certain individuals with a genetic predisposition toward a 'bad' neuroinflammatory response have neurodegeneration. But those with a genetic predisposition toward no inflammatory response, or a reduced one, are able to endure the pathology without marked neurodegeneration," he added.
The article, "Genetic modification of the relationship between phosphorylated tau and neurodegeneration," is published online in the journal Alzheimer's and Dementia.
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