A recent study conducted by researchers at Iowa State University may have identified the missing link between a metabolic gene and Alzheimer’s Disease, a connection that has eluded scientists for years. Led by Auriel Willette, an assistant professor of food science and human nutrition, the study concluded that family history can alter the behavior of TOMM40, explaining inconsistencies in previous research.
When TOMM40, or Translocase of Outer Mitochondrial Membrane-40kD, was first identified, it seemed clear certain behaviors of the gene significantly increased the risk of developing Alzheimer’s, but subsequent studies could not back up this claim. Instead of validation, conflicting data led many to believe the initial findings were wrong and the gene, which affects the way human cells produce energy, did not directly affect Alzheimer’s risk at all. Instead of dismissing the idea entirely, Willette decided to take a closer look at factors that could be producing the mixed results.
Using data from the Wisconsin Registry for Alzheimer’s Prevention and the Alzheimer’s Disease Neuroimaging Initiative, the ISU team decided to focus their research on individuals with a family history of Alzheimer’s, specifically those with parents who had been diagnosed with the degenerative condition. Looking at several different factors, they found that family history makes a big difference in how TOMM40 and the way brain cells react when they do not produce enough energy affects memory and thinking, especially as a person ages.
Looking at the length of one portion of the gene the team was surprised to find that, if the portion was longer in a person with no family history of Alzheimer’s, their risk for developing the disease was lowered by as much as one fifth. However, if the portion is the same length in a person who does have a family history of Alzheimer’s, their risk is increased, and symptoms like memory loss are likely to worsen much faster than they do in individuals with the shorter version of the gene, family history or not. With this conclusion, it seems a history of Alzheimer’s greatly influences the way TOMM40 affects brain cells and the progression of degeneration.
While some may wonder what practical use these findings may provide, it’s important to look at the results as one piece of a larger puzzle. Willette and the ISU researchers hope their work, by helping to solve a mystery that had previously puzzled other scientists, will help others with their own studies. Their hope is that eventually, by continuing to figure out how and why Alzheimer’s develops, together scientists can create better treatments and perhaps even discover a cure.
“It’s like trying to solve The New York Times Saturday crossword puzzle, which can be incredibly frustrating. But by finding the correct answer to one question, you can begin to fill in other answers,” Willette said, in an ISU video. “My hope is we’re providing the answer to that crossword and other researchers can find additional answers based off this one.”