Spotting Alzheimer’s early

Proteome Sciences, King’s College London take one small step toward overcoming early-onset Alzheimer’s by 2025

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COBHAM, England—Aimed at discovering new drugs to stem the tide of early-onset Alzheimer’s disease by 2025, U.K.-based biotechnology firm Proteome Sciences and King’s College London have joined hands to develop a blood test to predict which individuals are most likely to develop the degenerative disease—even before memory loss sets in.
There is no cure for Alzheimer’s disease, but researchers believe that a blood test to identify individuals at risk for contacting Alzheimer’s is not far away.
In research regarding blood analysis by Proteome Sciences and King’s College London, the two entities found, as they reported in the July 8 issue of Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, a set of 10 proteins in the blood identified as being able to predict the onset of Alzheimer’s disease. The study, which analyzed samples from more than 1,000 individuals, is reportedly the largest of its kind to date, marking a significant step toward developing an accurate diagnostic test for the disease.
While the cost of the project has not been disclosed, the study is the result of an international collaboration led by King’s College London and Proteome Sciences and funded by Alzheimer’s Research UK, the United Kingdom’s Medical Research Council and National Institute for Health Research, the Maudsley Biomedical Research Centre and Proteome Sciences.
Researchers used data from three international studies. Blood samples from a total of 1,148 individuals (476 with Alzheimer’s disease, 220 with mild cognitive impairment [MCI] and 452 elderly controls without dementia) were analyzed for 26 proteins previously shown to be associated with Alzheimer’s disease. A subgroup of 476 individuals across all three groups also had magnetic resonance imaging brain scans.
Researchers identified 16 of these 26 proteins as being strongly associated with brain shrinkage in either MCI or Alzheimer’s. They then ran a second series of tests to establish which of these proteins could predict the progression of people whose symptoms went from MCI to Alzheimer’s. Finally, researchers identified a combination of 10 proteins capable of predicting whether individuals with MCI would develop Alzheimer’s disease within a year, with an accuracy of 87 percent.
Simon Lovestone, senior author of the study from the University of Oxford, who led the work while at King’s College, stated: “Alzheimer’s begins to affect the brain many years before patients are diagnosed with the disease. Many of our drug trials fail because by the time patients are given the drugs, the brain has already been too severely affected.”
 “A simple blood test could help us identify patients at a much earlier stage to take part in new trials and hopefully develop treatments which could prevent the progression of the disease,” Lovestone added. “The next step will be to validate our findings in further sample sets to see if we can improve accuracy, reduce the risk of misdiagnosis and develop a reliable test suitable to be used by doctors.”
Although there is still much work to do, researchers believe the joint study is a step in the right direction toward an effective treatment or even a cure for Alzheimer’s disease, the most common form of dementia—a term for a decline in mental ability severe enough to interfere with daily life.
Globally, it is estimated that 135 million people will have dementia by 2050. In 2010, the annual global cost of dementia was estimated at $604 billion, according to Proteome Sciences.
One of the first signs of Alzheimer’s is MCI. This includes problems with day-to-day memory, language and attention, and can be an early sign of dementia or a symptom of something else, such as stress or anxiety. Approximately 10 percent of people diagnosed with MCI develop dementia within a year, researchers have stated. But apart from regular assessments to measure memory decline, there is currently no accurate way of predicting who will or won’t develop dementia.
“This is welcome research on an issue we’ve made a national priority,” U.K. Secretary of State for Health Jeremy Hunt stated in a news release. “Developing tests and biomarkers will be important steps forward in the global fight against dementia as we search for a cure.”
Christopher Pearce, CEO of Proteome Sciences, said research “is at an advanced stage following our disclosure last summer of excellent results showing positive predictive accuracy of 94 percent in Alzheimer’s disease and 88 percent in mild cognitive impairment (MCI)—and brings the prospects of a blood test significantly closer.”
 “We are also strongly encouraged by the news from our collaboration with researchers at King’s College London for making a significant step in developing a test which could allow doctors to detect Alzheimer’s at an early stage before any noticeable warning signs,” Pearce continued. “Out of tens of thousands of proteins in blood, the group has identified 10 on results from over 1,000 individuals that they believe could be used to identify Alzheimer’s, and we await further results with great interest.”
At Proteome Sciences “we firmly believe the use of protein biomarkers and related proteomics technologies has a vital role to play in finding the means to successfully diagnose early and treat what is one of the most distressing and debilitating diseases of our time—and that our contribution will be pivotal in that process,” Pearce concluded.
At the Pre G8 Dementia Summit in the United Kingdom on Dec. 10, 2013, U.K. Prime Minister David Cameron stated, “There is hope. I see it in the extraordinary work of U.K. life-sciences companies like Proteome Sciences, working with others to develop new tests for Alzheimer’s disease.”
Dr. Abdul Hye, lead author from the Institute of Psychiatry at King’s College London, stated: “Memory problems are very common, but the challenge is identifying who is likely to develop dementia. There are thousands of proteins in the blood, and this study is the culmination of many years’ work identifying which ones are clinically relevant. We now have a set of 10 proteins that can predict whether someone with early symptoms of memory loss or mild cognitive impairment will develop Alzheimer’s disease within a year, with a high level of accuracy.”
Dr. Eric Karran, director of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, stated: “As the onset of Alzheimer’s is often slow and subtle, a blood test to identify those at high risk of the disease at an early stage would be of real value. Detecting the first signs of Alzheimer’s could improve clinical trials for new treatments and help those already concerned about their memory, but we’re not currently in a position to use such a test to screen the general population.”
“With an aging population and age the biggest risk factor for Alzheimer’s, we are expecting rising numbers of people to be affected over the coming years,” Karran added. “It’s important to develop new ways to intervene early in the disease to help people maintain their quality of life for as long as possible.”
Dr. Ian Pike, chief operating officer of Proteome Sciences and co-author of the July 8 journal article, stated: “By linking the best British academic and commercial research, this landmark study in Alzheimer’s disease is a major advance in the development of a simple blood test to identify the disease before clinical symptoms appear. This is the window that will offer the best chance of successful treatment. Equally important, a blood test will be considerably easier and less expensive than using brain imaging or cerebrospinal spinal fluid.”
Proteome Sciences is in the process of selecting commercial partners to combine the protein biomarkers in a blood test for the global market, “a key step forward toward delivering effective and early treatment for this crippling disease,” Pike added.
James Pickett, head of research at the Alzheimer’s Society, has cautioned that a blood test for dementia is not just around the corner, noting that accuracy would need to be improved before it could be a useful diagnostic test.
The next step for the joint study will be to validate the 10-protein test and reduce the risk of misdiagnosis by much more extensive clinical testing over the next two or three years, he said.

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