A protein has been discovered in the blood of people who go on to develop mild cognitive impairment several years later. Dr. Steven Kiddle of King’s College London, UK, and colleagues explain there currently are no treatments that can reliably prevent mild cognitive impairment, which can progress into Alzheimer’s disease.
Prevention studies are hampered because, while magnetic resonance imaging (MRI) and positron emission tomography (PET) brain scans can display signs of the disease before the symptoms begin, the scans are expensive. So the team set out to identify blood markers which may indicate an individual’s future risk of mild cognitive impairment.
Their study took blood from over 100 sets of healthy twin volunteers, of whom 55 were identical twin-pairs, and measured over 1,000 proteins in the samples. They used a protein biomarker discovery tool, and assessed each individual’s cognitive ability over the next 10 years.
For these cognitive tests, the paired associates learning part of the CANTAB cognition battery was used, as it is thought to be more sensitive to early Alzheimer’s disease-related changes in cognition than the popular mini mental state examination.
Results suggested that blood levels of a protein called MAPKAPK5 tended to be lower in those whose cognitive ability declined. Findings are published in the journal Translational Psychiatry.
The authors say that a plasma protein biomarker measured in a single blood sample could be more practical in some settings than cognitive testing over a 10-year period in healthy older adults. They point out that the use of twins in the study allows them to show that the link between MAPKAPK5 and decline in cognitive ability was independent of age and genetics.
“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,” said Dr. Kiddle.
“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.”
Kiddle told the British Broadcasting Corporation, “People think it may be hard to reverse 20 years of potential damage to your brain. But if you could start much earlier in that process, then you might be able to find something that works.” However, he cautioned, “A test you could go in to your doctor to say, ‘Do I have Alzheimer’s disease or not?’ I think that’s a long way off.”
Dr. Claire Steves, a co-author of the study, 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.”
Previous to this study, MAPKAPK5 has mostly been investigated in relation to cancer and rheumatoid arthritis, rather than Alzheimer’s. Earlier work in twins suggests that MAPKAPK5 levels are mostly affected by non-shared environmental factors.
These tend to be more modifiable than many aspects of the twins’ shared environment such as maternal and family factors. “Given our findings, we hypothesize that MAPKAPK5 may be a biomarker of modifiable cognitive ageing,” the researchers believe.
“Selection of individuals for intervention studies whose risk is modifiable may lead to improved outcomes,” they state. MAPKAPK5 levels may “convey information on cognitive ability that is complementary to genetic markers, and may be a biomarker of modifiable cognitive ageing,” they conclude. But first, further studies will be needed to confirm the link.
The number of dementia cases are expected to triple globally by 2050. As it can take more than a decade from the first changes in the brain to culminate in symptoms such as memory loss, confusion and personality change, pharmaceutical therapies may have to be started years before symptoms appear, in order to protect the brain.
Commenting on the study, Dr. Eric Karran of the charity Alzheimer’s Research UK, said, “It will be necessary to investigate more about a possible mechanism linking this protein to changes in memory and thinking. 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.”
Kiddle, S. et al. Plasma protein biomarkers of Alzheimer’s disease endophenotypes in asymptomatic older twins: early cognitive decline and regional bran volumes. Translational Psychiatry, 16 June 2015 doi:10.1038/tp.2015.78