Research led by the Institute of Psychiatry at King’s College London, and published in the Archives of General Psychiatry, has found that blood levels of the protein clusterin could be an early biomarker of Alzheimer’s disease (AD), many years before symptoms appear.

Comparing blood samples and brain scans of 300 research participants with AD, mild cognitive impairment or normal cognition, the team of scientists found that increased levels of a single protein - clusterin – were related to brain shrinkage, severity of memory problems and a risk of faster memory loss shown on the brain scans many years later. These findings could lead to the development of a blood test to identify who would benefit from early treatment of AD and also whether treatments were working to delay or prevent brain damage.

Using the same method in blood samples from volunteers in an ongoing study in the United States, the researchers also 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, researchers discovered increased levels of clusterin in the blood of mice with AD, as they were ageing. Under the microscope, they observed clusterin to be surrounding the amyloid plaques in the mice’s brain, indicating that clusterin might work to help protect the brain from amyloid protein. This finding from proteomics complements the discovery reported last year by an international team including the King’s 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.

Developing an inexpensive, easy test

Lead author Dr Madhav Thambisetty, formerly of the Institute of Psychiatry at King’s 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 King’s 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.’

The ’Holy Grail’ of dementia research

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.’

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.’

This research was made possible by funders including the Alzheimer’s Research Trust and the NIHR, and by the founders of the ground breaking academic-industry collaboration, the Innovative Medicines Initiative (IMI).

Biomarker closer for Alzheimers disease

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Biomarker closer for Alzheimers disease