ultrasound alzheimers genetic variant

Study: A Genetic Variant That May Cause Alzheimer’s

By | September 22nd, 2020

Every participant in a new study had the biomarkers of Alzheimer's, but almost half — 49 percent — of people with a certain genetic variant had Alzheimer's dementia, compared to 29 percent of those without the variant.

Protein plaques and tangles have long been thought to be the cause of Alzheimer’s disease. Now, scientists are looking beyond those biomarkers at a certain genetic variant that could be a clue to what jumpstarts Alzheimer’s related cognitive decline. According to new research published in the journal Neurology, the genetic variation, found on the sixth chromosome, leads to changes in the metabolism of an an antioxidant called glutathione. The researchers believe these changes could be associated with thinning of the cerebral cortex, the brain’s control center and information-processing hub, responsible for brain functions like memory, association and thinking.

What to learn more about what genes are suspected to cause Alzheimer’s? Explore the issue in our interactive guide

“Our study identified one significant single nucleotide polymorphism related to cognitive decline independent of amyloid-beta and tau protein deposits in the brain,” Dr. Yong Jeong, a study author from the Korea Advanced Institute of Science and Technology, said in a 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.”

Is Alzheimer’s genetic?

Short answer: It’s complicated! Many genes increase Alzheimer’s risk by some measure. Some genes increase risk by quite a lot. But overall, genetics is only part of the story.

Breakthrough advancements in gene-sequencing technologies have opened up new pathways for understanding health and disease. Scientists can sequence our genetic code to search for genes involved in diseases. In some cases, genes are the key to what causes a disease. For example, carriers of genes like ApoE4, TREM2 and others are thought to have dramatically higher Alzheimer’s risk (at least in some racial groups).  

But the more we probe genetics and disease, the more we are learning that when it comes to the majority of diseases and conditions — including Alzheimer’s — a few genes aren’t going to solve the mystery.

Which genes increase Alzheimer’s risk?

While detecting new genes with Alzheimer’s links can make a big news story, about five out of every one hundred cases are attributed to our genetics.

Alzheimer’s is characterized by the deposition of amyloid plaques and tau neurofibrillary tangles in the brain. Some of our genes, or gene mutations, are involved in development and clearance of amyloid plaques. Carrying these genetic markers increases the risk of developing Alzheimer’s. These include PSEN1 and variations on TREM2.

So, does this mean Alzheimer’s is definitely caused by a specific gene or gene variant? Not quite: The roles of amyloid and tau in Alzheimer’s disease are still shrouded in mystery. And complicating things further, in the other 95 percent of cases, genes don’t drive the disease. They may be part of the story, but their interactions with other aspects of our biology, aging, and the environment are all in play.

What did this study find?

Genetic variants have been found in past research to protect people against the effects of amyloid and tau protein build-ups in the brain. One extremely rare genetic variation was recently found to protect a woman against the onset of symptoms from Alzheimer’s for several decades. Jeong’s research team suspects this variant may do the opposite.

The researchers studied a group of 486 people who all had deposits of beta-amyloid and tau — two problematic proteins that are linked to Alzheimer’s — in their brains. Some had normal thinking and memory skills, while others had mild cognitive impairment, and yet others had symptomatic Alzheimer’s.

Some performed worse on cognitive tests than others. Those poor performers all shared one thing that the rest of the group did not: a certain genetic variant. Researchers used genetic analysis to pinpoint gene variants that were associated with cognitive function independent of amyloid and tau.

On a cognitive test where the highest score was 30, those with the genetic variant scored an average of 25. Those without the variant had an average score of 27. Among those with the variant, 11 percent had normal cognition, compared to a quarter of those without the variant who had normal cognition. Almost half — 49 percent — of people with the variant had Alzheimer’s dementia, while only 29 percent of those without the variant had Alzheimer’s dementia.

To measure the thickness of each person’s brain cortex, a common measure of brain health, researchers looked at brain scans. People who did not have the genetic variation, on average, had a greater cortical thickness than the people who have the genetic variation.

“Deposits of amyloid-beta 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.”

Genetic variations — or single nucleotide polymorphisms — are common enough to serve as potential biomarkers that may help identify genes that linked to diseases. One of this study’s limitations was a small sample size; researchers say more study of this particular genetic variant as it relates to Alzheimer’s is in needed.

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