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Researchers find biomarker associated to early pathology and symptoms of Alzheimer's disease

05 July 2010

Research led by the Institute of Psychiatry (IoP) King’s College London (KCL), and published in the Archives of General Psychiatry today, has found that clusterin levels in blood could be an early biomarker of Alzheimer’s disease (AD) many years before symptoms appear. The international team of scientists also found that higher levels of clusterin were related to more severe and rapid memory loss and greater brain shrinkage. Their findings could lead to development of a blood test to help identify who would benefit from early treatment of AD and also whether treatments were working to delay or prevent brain damage.

Researchers have been focusing on developing an inexpensive blood test that will accurately reflect the damage detected by brain scans in patients in the early stages of AD, such as shrinkage ('atrophy') in certain regions and abnormal accumulations of a protein called beta amyloid.

In this study, researchers used a novel strategy combining brain scans with proteomics, a method that can detect hundreds of proteins in a single blood sample. They compared blood samples and brain scans of 300 research participants with AD, mild cognitive impairment or normal cognition. They found that a single protein - clusterin – was related to brain shrinkage, severity of memory problems and a risk of faster memory loss.  Using the same method in blood samples from volunteers in an ongoing study in the United States, they showed that increased amounts of clusterin, measured a decade earlier to the brain scans, were linked to higher levels of beta amyloid in the brain.

Finally, in mouse models of AD, researchers discovered increased levels of clusterin in the blood as the mice aged. Under the microscope, they also observed clusterin to be surrounding the amyloid plaques. This provides further evidence that clusterin is critically important in Alzheimer’s disease where it probably works to help protect the brain from amyloid protein. This finding from proteomics complements the discovery reported last year by an international team including the KCL group that showed the clusterin gene increased risk of AD – a finding noted by Time magazine as one of the top ten medical discoveries of 2009.

First author Dr.Madhav Thambisetty, formerly of the IoP KCL UK and now with the National Institute on Aging, National Institutes of Health, US, said:  'A primary goal in Alzheimer’s research is to develop an inexpensive, easily administered test to accurately detect and track the progression of this devastating disease. Identifying clusterin as a blood biomarker that may be relevant to both the pathology and symptoms of the disease may bring us closer to this goal.'

The head of the research group, Professor Simon Lovestone, Director of the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) for Mental Health at South London and Maudsley NHS Foundation Trust (SLaM) and KCL continues:  'Our results add further evidence to the role of clusterin in AD and though not a test in itself we hope these findings will be taken up by other research groups and if confirmed independently, will help us conclude that clusterin levels in blood are truly a marker of disease pathology in patients with AD.'

Rebecca Wood, Chief Executive of the Alzheimer’s Research Trust (ART), said: 'A simple blood test for detecting Alzheimer’s has long been the holy grail for dementia researchers and these new findings edge us closer in the search. Early detection of dementia will be crucial to ensuring the treatments of the future can be given swiftly and when most effective.  Research is the only answer to dementia, yet our scientists remain in desperate need of funds. Investing in research now will bring the treatment breakthroughs we so urgently need in a world where 35 million live with this devastating condition.'

This research was made possible by funders including the UK’s Alzheimer’s Research Trust and the NIHR, and by the founders of the ground breaking academic-industry collaboration, the Innovative Medicines Initiative (IMI).  The main part of this study was the IMI pilot project AddNeuroMed which serves as a prime example of how industry and academia can work together toward patient benefit.

Dr Michel Goldman, Executive Director, IMI said:  'These findings demonstrate the importance of public-private collaboration in complex fields like Alzheimer’s research. The scientific challenges in pharmaceutical R&D clearly require novel collaborative approaches.  Therefore the Innovative Medicines Initiative actively  builds open innovation  networks between public and private partners for the ultimate benefit of patients.'

Professor Lovestone concludes: 'This study is particularly exciting as it represents what can really be achieved when industry and academia work hand in hand and demonstrates the potential of true partnership working.'

Association of Plasma Clusterin Concentration With Severity, Pathology, and Progression in Alzheimer Disease – Thambisetty et al  Arch Gen Psychiatry. 2010;67[7]:739-748.



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