Family History of Alzheimer’s May Explain Link of Metabolic Gene that Raises Risk for Disease

Years of conflicting research that failed to pinpoint the missing link between a mitochondrial gene and the risk of Alzheimer’s may have finally been resolved by the scientists of Iowa State University (ISU) in the U.S. The researchers say that family history of Alzheimer's disease may be the missing link. It shows that having a family history of Alzheimer's disease appears to alter the behavior of the gene called TOMM40.

Lead researcher AurielWillette, assistant professor of food science and human nutrition at ISU, says the initial discovery of the gene TOMM40 gave the scientists impression that it raises the risk of Alzheimer’s. But the findings were later dismissed when several studies failed to replicate the results.

However, Willette and his colleagues weren’t convinced that the gene was a total failure, so they decided to examine other elements that may be producing the mixed results.

The researchers discovered a startling difference in the gene’s effect on cognitive function, memory and risk based on a family history of Alzheimer’s disease and the length of a specific part of the gene.

“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.

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“However, if your mom or dad has Alzheimer’s, then having a long version is bad. It’s a complete polar opposite.”

The main pathological hallmarks ofAlzheimer’s disease are amyloid-β (Aβ) plaques, and neurofibrillary tangles, caused by tau protein. These plaques and tangles around the neurons eventually cause the neurons to die.

Outward symptoms start with mild memoryloss. As the symptoms progress, the person finds it increasingly difficult to hold a conversation or carry out everyday tasks such as button a shirt.

Although numerous studies being conducted worldwide are providing new clues, scientists still do not know the exact causesof Alzheimer's disease. They think that there are various factors, and some of these affect different people in different ways, according to the study.

Family history of Alzheimer’s and TOMM40

The researchers designed the study to explore the magnitude to which family history regulated the effects of TOMM40 on symptoms of Alzheimer's disease, such as thinking and memory loss.

They used data from two large studies of Alzheimer's disease. One set of data came from 912 adults in the Wisconsin Registry for Alzheimer's Prevention – a study which is following middle-aged adults at risk of developing Alzheimer's and following changes in cognitive function and memory loss, based on assessments carried out every 2 years for up to a decade.

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The other set of data came from 365 participants in the Alzheimer's Disease Neuroimaging Initiative – a study which is monitoring similar changes in older adults with and without the disease.

The researchers found that having a family history of Alzheimer's disease appears to make a big difference in how TOMM40 affects memory and thinking, and that the difference depends on the length of a particular portion of the gene. [Read more Study:Access to nature makes men and seniors sleep better]

Prof. Willette and his team found that having the longer version of the gene, together with no family history of Alzheimer's, was linked to around a one-fifth lower risk of developing Alzheimer's disease and better memory up to 10 years later.

Family history was focused particularly on whether Alzheimer’s disease was found in a participant’s parents. The researchers also discovered a link between the family history, gene, and mitochondrial function, which produces energy to power the cells. Age, gender and education were controlled for in the examination of TOMM40 gene and family history in the participants.

The team is also involved in another project which is investigating factors that affect how the body makes and uses energy, such as insulin resistance, as well as proteins and enzymes that affect energy regulation.

Studies like these are slowly uncovering what happens to thinking and memory when there is not enough energy for brain cells to perform properly.

The study was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.