Blood protein discovered that can predict 10-year cognitive decline

Posted on 16th June 2015

Researchers based at King’s College London have joined forces with other scientists across the world to discover a protein in blood that appears to predict 10-year decline in memory and thinking skills in healthy people.

The findings provide new opportunities to understand the mechanisms controlled by the protein, as well as investigate whether it could be a clinically useful diagnostic marker for early Alzheimer’s disease. The study was funded in part by the Medical Research Council (MRC), Alzheimer’s Research UK, Wellcome Trust and the National Institute for Health Research.

The study, led by researchers at the MRC Social, Genetic and Development Psychiatry Centre, analysed blood samples in 55 pairs of identical twins. The twins were taking part in a wider study called TwinsUK and also had taken a memory and thinking test in 1999 and in 2009. The researchers looked for changes in the levels of proteins that might correlate with changes in cognitive function over the ten-year period.

The researchers discovered that the level of a protein called MAPKAPK5 was associated with ten-year change in scores on the memory and thinking test. Those volunteers with lower levels of the protein in their blood tended to have a larger change in their test score over the follow-up period, indicating a faster decline in their memory and thinking skills.

The team also looked at brain scans provided by the twins, as well as 254 healthy volunteers from a second ongoing study who had provided blood samples and had MRI brain scans. The team identified three proteins in the twin pairs which seemed to associate with the size of areas of the brain linked to Alzheimer’s. One of these proteins, called MAP2K4 was also found to be associated with the size of an area of the brain called the left entorhinal cortex in non-twin volunteers.

The study is one of the first of its kind to search for blood markers of cognitive decline in twins, removing the impact of age and genetics. The findings identify a number of proteins that researchers can investigate further as predictive markers of environmentally-influenced and potentially modifiable cognitive decline in the healthy population.

Dr Eric Karran, Director of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity said:

“Searching for reliable markers of disease in the blood is a tricky task, as protein levels can be influenced by so many factors that differ between individuals. Twin studies present a unique insight into the biology of complex diseases like Alzheimer’s, as they control for age and most genetic effects. This study associated blood levels of protein called MAPKAPK5 with cognitive decline over a ten year period, but it will be necessary to investigate more about a possible mechanism linking this protein to changes in memory and thinking. The study did not look at Alzheimer’s, so longer follow-up will be needed to see whether the protein could also predict a future diagnosis of the disease in this group of people.

“Current diagnosis of diseases like Alzheimer’s is not an exact science and we urgently need to improve approaches to deliver more timely and accurate diagnosis. Accurate and early diagnosis of Alzheimer’s will be essential for the development of new treatments, allowing clinical trials to take place involving the right people at the right time, when those treatments are most likely to be effective. A diagnostic marker in blood could provide a valuable non-invasive and cost-effective addition to the current tests available, but much more work needs to be done to build on these findings before we could see them being used routinely to aid Alzheimer’s diagnosis in the clinic.”

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