Study in twins finds blood protein that may indicate risk of Alzheimer’s disease

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Study in twins finds blood protein that may indicate risk of Alzheimer’s disease (MRC press release).

Study led by Dr Steven Kiddle of the Bioinformatics core.

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 55 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 a computerised test, 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.

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.

*SOMAscan is a trademark of SomaLogic, Inc.

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, is published here.


The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Thirty-one MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. 

The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government’s strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. 

NIHR Biomedical Research Centres (BRCs) are partnerships between England’s leading NHS organisations and universities with the aim of conducting translational research to transform scientific breakthroughs into life-saving treatments for patients. NIHR BRCs are leaders in translating lab-based discoveries into new cutting edge treatments, technologies, diagnostics and other interventions in clinical settings. BRCs host research themes across a range of disease and therapeutic areas.

The Wellcome Trust is a global charitable foundation dedicated to improving health. We support bright minds in science, the humanities and the social sciences, as well as education, public engagement and the application of research to medicine. Our investment portfolio gives us the independence to support such transformative work as the sequencing and understanding of the human genome, research that established front-line drugs for malaria, and Wellcome Collection, our free venue for the incurably curious that explores medicine, life and art.

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