New research from the US reveals that a common variant of the FTO obesity gene carried by more than one third of Americans that causes them to gain weight and puts them at risk for obesity, also leads to loss of brain tissue, thereby increasing their risk of developing neurodegenerative diseases like Alzheimer’s later in life.

The study, which was funded by the National Institutes of Health and private industry, appears in the early online issue of the Proceedings of the National Academy of Sciences and was led by researchers at the University of California Los Angeles (UCLA).

About three years ago we learned of a startling discovery: nearly half of Americans descended from Europeans carry a variant of the fat mass and obesity associated (FTO) gene that causes them to put on a few extra pounds of weight, measure one inch more around the waist, and even more alarmingly, also puts them at higher risk of obesity compared to non-carriers.

Now UCLA researchers have found that the same FTO variant, which is also present in around one quarter of US Hispanics and in 15 per cent of African Americans and Asian Americans, is linked with a loss of brain tissue, placing around one third of the American population at higher risk of diseases like Alzheimer’s.

Senior author Dr Paul Thompson, a UCLA professor of neurology, and two graduate students from his lab, lead authors April Ho and Jason Stein, and colleagues. used magnetic resonance imaging to make 3D maps of the brains of 206 healthy elderly people from 58 US locations participating in the Alzheimer’s Disease Neuroimaging Initiative, a large 5 year project that is looking at what helps the aging brain resist disease.

They found that participants who had the FTO variant had consistently less brain tissue than the non-carriers: 8 per cent less in frontal lobe tissue (the brain’s command and control centre) and 12 per cent less in occipital lobe tissue (the back part of the brain that controls vision and perception).

They also established that other obesity-related factors like cholesterol, diabetes and high blood pressure could not account for these differences.

Thompson, who is also a member of the Brain Research Institute and the Laboratory of Neuro Imaging at UCLA, described the results as “curious”. He told the press that:

“If you have the bad FTO gene, your weight affects your brain adversely in terms of tissue loss.”

And yet:

“If you don’t carry FTO, higher body weight doesn’t translate into brain deficits; in fact, it has nothing to do with it. This is a very mysterious, widespread gene,” said Thompson.

Thompson said half of the world’s population has this gene variant, and thus for them, any loss of brain tissue puts them at higher risk of functional decline.

But, shocking as this news is, it does not mean carriers of the variant are doomed, because as Thompson pointed out, they can still exercise and eat healthily to reduce their chances of developing obesity and brain decline: “a healthy lifestyle will counteract the risk of brain loss, whether you carry the gene or not,” he explained.

“So it’s vital to boost your brain health by being physically active and eating a balanced diet,” said Thompson.

Thompson also said that the discovery “will help to develop and fine tune the anti-dementia drugs being developed to combat brain aging”.

“A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly.”
PNAS, published ahead of print 19 April 2010.
DOI:10.1073/pnas.0910878107

Source: UCLA.

Written by: Catharine Paddock, PhD