Study explores genetics behind Alzheimer's resiliency

May 2, 2014

Autopsies have revealed that some individuals develop the cellular changes indicative of Alzheimer's disease without ever showing clinical symptoms in their lifetime.

Vanderbilt University Medical Center memory researchers have discovered a potential genetic variant in these 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," said 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.

The article, "Genetic modification of the relationship between and neurodegeneration," was published online recently in the journal Alzheimer's and Dementia.

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 ," Hohman said.

"It appears that certain individuals with a 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."

Hohman hopes to expand the study to include a larger sample and investigate gene and protein expression using data from a large autopsy study of Alzheimer's disease.

"The work highlights the possible mechanism behind asymptomatic Alzheimer's disease, and with that mechanism we may be able to approach intervention from a new perspective. Future interventions may be able to activate these innate response systems that protect against developing Alzheimer's symptoms," Hohman said.

Explore further: Genetic markers ID second Alzheimer's pathway

Related Stories

Genetic markers ID second Alzheimer's pathway

April 4, 2013

Researchers at Washington University School of Medicine in St. Louis have identified a new set of genetic markers for Alzheimer's that point to a second pathway through which the disease develops.

Brain cell activity regulates Alzheimer's protein

February 26, 2014

Increased brain cell activity boosts brain fluid levels of a protein linked to Alzheimer's disease, according to new research from scientists at Washington University School of Medicine in St. Louis.

Chronic sleep disturbance could trigger onset of Alzheimer's

March 18, 2014

People who experience chronic sleep disturbance—either through their work, insomnia or other reasons—could face an earlier onset of dementia and Alzheimer's, according to a new pre-clinical study by researchers at Temple ...

Recommended for you

Predicting change in the Alzheimer's brain

October 6, 2015

MIT researchers are developing a computer system that uses genetic, demographic, and clinical data to help predict the effects of disease on brain anatomy.

Old drug offers new hope to treat Alzheimer's disease

September 21, 2015

Scientists from the Gladstone Institutes have discovered that salsalate, a drug used to treat rheumatoid arthritis, effectively reversed tau-related dysfunction in an animal model of frontotemporal dementia (FTD). Salsalate ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.