Neurology: BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer’s Prevention
Researchers in the US have studied people at risk of developing Alzheimer’s disease and found that a particular version of a gene called BDNF is associated with a decline in memory and thinking skills. The results are published today (3 May) in the journal Neurology.
Brain-derived neurotrophic factor (BDNF) is a protein that works in the brain to promote the growth of nerve cells and support the connections formed between them. The BDNF gene provides the instructions for cells to make the protein and comes in slightly different versions, called ‘Val’ and ‘Met’. We each have two copies of the gene and while many people have two Val copies, previous research has suggested that having one or two copies of the Met version may alter the way the brain is structured and a person’s memory and thinking skills. In this new study, a team of researchers in the US set out to explore the links between having either Val or Met versions of the BDNF gene and memory and thinking skills.
The team worked with participants from the Wisconsin Registry for Alzheimer’s Prevention, a long-running study of people between the ages of 40 to 65 years. Of the 1,023 people who were included in the study, 64% had at least one parent who had developed Alzheimer’s, meaning that the group as a whole were more likely to develop the disease than the general population. None of the participants had problems with their memory and thinking skills at the start of the study.
Over an average of seven years, each participant took part in up to five assessments of memory and thinking ability, and provided a blood sample which researchers tested for the different versions of the BDNF gene. A subset of 140 participants also had brain scans to measure levels of amyloid protein, which is known to build up in the brains of people with Alzheimer’s and can begin doing so years before people develop dementia symptoms. The brain scans were performed on average six years after the participants attended their first assessment.
The researchers found that having at least one Met copy of the BDNF gene was linked with a greater overall decline in memory and thinking skills during the course of the study. However, not all aspects of cognitive ability declined more sharply in people with a MET version. In addition, at the beginning of the study, participants with this form of the BDNF gene performed better in certain tests including those for verbal learning and memory, and speed and flexibility in thinking skills.
The participants that received brains scans were classed as being either amyloid positive or amyloid negative, and the researchers found that this altered the course of changes in memory and thinking over time. People who were classed as being amyloid negative did not show changes in verbal learning and memory over time, regardless of whether they carried a copy of the Met BDNF gene. However, carrying at least one copy of the Met BDNF gene and having an amyloid positive brain scan was linked with a greater decline in verbal learning and memory.
Dr David Reynolds, Chief Scientific Officer at Alzheimer’s Research UK, said:
“Our genes give rise to the small differences that make us all unique. While most of these differences are completely benign, some can lead to changes in our risk for a number of diseases, including Alzheimer’s.
“This study has drawn links between a brain growth factor called BDNF and memory and thinking skills, suggesting that certain versions of the BDNF gene could be linked with a more rapid decline in memory and thinking as we age. As the researchers did not measure the actual levels of BDNF in the brain, it is difficult to draw any firm conclusions about its effect.
“While the researchers followed a large number of people over several years, they did not examine whether people with different versions of the BDNF gene went on to develop dementia, and it is not possible to tell whether the gene could alter the risk of the condition. Future research will need to repeat this study in groups that more accurately mirror the general population, as well as further exploring the links between BDNF and memory to see whether there could be other factors at play here.”
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