CANTAB study identifies blood protein MAPKAPK5 that may indicate cognitive decline

Posted on 1 May 2015 in Research

Scientists have identified a single blood protein that may indicate the development of Mild Cognitive Impairment (MCI) years before symptoms appear, a disorder that has been associated with an increased risk of Alzheimer's disease or other dementias.

The research, published today in Translational Psychiatry, used data from over 100 sets of twins from TwinsUK, the biggest adult twin cohort in the UK. The use of 93 identical twin-pairs in the study allowed researchers to show that the association between the blood protein and a ten year decline in cognitive ability was independent of age and genetics, both of which are already known to affect the risk of developing Alzheimer’s disease, the most common form of dementia.

The study, the largest of its kind to date, measured over 1,000 proteins in the blood of over 200 healthy individuals using a laboratory test called SOMAscan*, a protein biomarker discovery tool that simultaneously measures a wide range of different proteins. Using CANTAB PAL, the researchers then assessed each individual’s cognitive ability, and compared the results with the measured levels of each different protein in the blood. For the first time, they found that the blood level of a protein called MAPKAPK5 was, on average, lower in individuals whose cognitive ability declined over a ten year period.

“The use of longitudinal change in CANTAB-PAL, a cognitive test that is sensitive to early cognitive decline, was critical in the discovery of MAPKAPK5 as a potential biomarker relevant to AD. This demonstrates the importance of studying decline in cognitive abilities using sensitive tests in asymptomatic older adults.”

There are currently no treatments available proven to prevent Alzheimer’s disease, and prevention trials for Alzheimer’s disease can be problematic because to be effective, they must involve individuals at risk of the disease, who can be hard to identify. Studies using Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) brain scans have been shown to display visible signs of the disease before the onset of symptoms, but these types of scans are both timely and costly.

To date, few other studies have looked at the blood of individuals with very early stages of cognitive decline and therefore most appropriate for a prevention study. Identifying blood markers such as MAPKAPK5, which may indicate a person’s future risk of Alzheimer’s disease, could contribute towards the better design of prevention trials.

Dr Steven Kiddle, lead author and Biostatistics Research Fellow at the Medical Research Council (MRC) Social, Genetic & Developmental Psychiatry Centre at King’s College London, said: “Although we are still searching for an effective treatment for Alzheimer’s disease, what we do know is that prevention of the disease is likely to be more effective than trying to reverse it. The next step will be to replicate our finding in an independent study, and to confirm whether or not it is specific for Alzheimer’s disease, as this could lead to the development of a reliable blood test which would help clinicians identify suitable people for prevention trials.”

Co-author, Dr Claire Steves, Geriatrician and Senior Lecturer in Twin Research at King’s College London, added: “We’re very optimistic that our research has the potential to benefit the lives of those who don’t currently have symptoms of Alzheimer’s, but are at risk of developing the disease.”

The research was funded by the Medical Research Council (MRC), the National Institute of Health Research (NIHR) Biomedical Research Centre for Mental Health and the Wellcome Trust.

The paper, entitled ‘Plasma protein biomarkers of Alzheimer’s disease endophenotypes in asymptomatic older twins: early cognitive decline and regional bran volumes’, by Kiddle et al. was published in Translational Psychiatry today

Edited from MRC Press Realease 16th June 2015.