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Mitochondrial Gene Length & Family History Influence Alzheimer’s Disease Risk

Mitochondrial Gene Length & Family History Influence Alzheimer’s Disease Risk

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  • Alzheimer’s disease (AD) is a neurodegenerative disease and its exact cause still remains shrouded in mystery.
  • Current study identifies positive family history to be a vital link in increasing the risk of AD in persons with increased length of a portion of the mitochondrial gene, TOMM40.

Mitochondrial Gene Length & Family History Influence Alzheimer’s Disease Risk

Positive family history may increase the risk of development of Alzheimer's disease (AD) within 10 years in late middle-aged persons if they have a longer version of the TOMM-40 mitochondrial gene, according to a new Iowa State University study, led by Auriel Willette, an ISU assistant professor of food science and human nutrition.

TOMM40 Gene and Alzheimer's Disease - Conflicting Data

Earlier research on the role of TOMM-40 gene in AD yielded conflicting results. The initial study suggested a positive association between presence of TOMM40 gene and AD. However, subsequent research failed to reproduce the findings and the initial findings were therefore dismissed as insignificant.

However, Willette, lead author of the current research believed there might be something more to the TOMM gene and AD association and decided to investigate this further.


For the current study, Willette and his colleagues analyzed information obtained from the Wisconsin Registry for Alzheimer's Prevention study and the Alzheimer's Disease Neuroimaging Initiative. The Wisconsin group monitors alterations in memory and cognition over time in middle-aged people at risk for development of Alzheimer's. The other group follows up similar changes in older persons with and without the disease.

Willette says without this data, researchers would not have gained much insight.

Family History - The Crucial Link Between TOMM40 Gene and AD Association

In their study, Dr Willette and his team found a significant difference in the association between the presence of TOMM40 gene and AD when there was a positive family history of Alzheimer's disease.

The following notable findings emerged from the study.
  • Late middle-aged people with a positive family history along with concomitant longer version of the gene had twice as much memory impairment up to 10 years later in comparison to someone with a family history and a short version of the gene.
  • A similar but even stronger association was seen in a separate group of older adults with and without Alzheimer's.
  • The team also found a link between the gene, family history and mitochondrial function, which is critical as the energy producer for metabolic activities of the cell.
"It was kind of a shot in the dark, but we found if you don't have a family history of Alzheimer's disease, then having a longer version of the gene is a good thing. It is related to better memory up to 10 years later and about one-fifth of the risk for developing Alzheimer's disease," said Willette, who is also an adjunct assistant professor of neurology at the University of Iowa. "However, if your mom or dad has Alzheimer's, then having a long version is bad. It's a complete polar opposite."

The TOMM40 Gene - A Possible Piece In The Puzzle of Alzheimer's Disease

As findings from several research projects on Alzheimer's disease and insights into reducing the risk are emerging, it is evident that there could be multiple triggers for the development of AD.

The current study focuses chiefly on the importance of mitochondrial function and integrity in the maintenance of cognition, memory and effect on the brain cells. However, Willette has also analyzed insulin resistance, enzymes and proteins that cause problems in energy regulation.

"As researchers, it feels like we're on a train with a thousand different levers and buttons. We as a scientific community are trying to pull every lever and push every button to see which one is the brake," Willette said. "At the end of the day, this is all about better understanding how and how soon we get the disease. The hope is that knowing this will inform us about new steps we can take to slow down the progression."


According to Willette, the aim of Alzheimer's research is to delineate unifying factors that contribute to development of the disease by analyzing and piecing together changes seen in the blood, brain cells and other areas of the body. The team hopes that findings of the current study will help future research teams gain better insight into the disease.

Likening the various risk factors and triggers to clues for solving a crossword puzzle, he says, "My hope is we're providing the answer to that crossword and other researchers can find additional answers based off this one."

Source: Medindia

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