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Clusterin May Influence Alzheimer Development and Severity

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Reseachers from the Institute of Psychiatry at King's College London conducted clinical assessments and brain imaging scans, and analyzed blood plasma samples from people with either Alzheimer's disease, mild cognitive impairment (precursor to Alzheimer's), or no dementia.

Alzheimer's is the most common form of dementia -- a brain-wasting condition that affects around 35 million people around the world -- and despite decades of research, doctors still have few effective weapons against it.

Drugs can relieve some of the symptoms for a while, but patients gradually lose their memories, their ability to navigate and understand the world, and to care for themselves.

This research team used a technique called proteomics, which analyses proteins, to conduct two "discovery phase" studies in 95 patients and found that clusterin appeared to be linked with the early signs of Alzheimer's.

The researchers found an association between levels of clusterin in blood plasma and severity of Alzheimer's disease, rapid progression of Alzheimer's disease, and atrophy in an area of the brain called the entorhinal cortex, which plays a role in memory.

The researchers also concluded that high clusterin levels in blood plasma were linked with increased amyloid-beta (a protein that forms the brain plaques associated with Alzheimer's disease) in the brain's medial temporal lobe. Previous studies suggest that clusterins belong to a family of proteins called extracellular chaperones, which regulate the formation and removal of amyloid, said the researchers. 

"We found that this clusterin protein was increased in blood as much as 10 years before people had the signs of Alzheimer's disease in their brains," said Simon Lovestone, who led the study. "And even when they had signs of Alzheimer's disease in their brains, they still had no clinical signs of the disorder -- so this suggests that this is a really, really early change that occurs in people who are going to get Alzheimer's disease."

"Our findings clearly implicate clusterin, but there may well be other proteins in plasma related to the disease process, and indeed our previous studies and those of others suggest this is the case," the researchers concluded. "These results may have wider implications for the identification of other amyloid chaperone proteins in plasma, both as putative Alzheimer's disease biomarkers as well as drug targets of disease-modifying treatments."

Lovestone said it was important to stress there was still a lot more work to do before a test could be used by doctors in clinics, but said such a technique may in future become part of a range of tests to find people with early signs of the disease. The researchers said that while doctors are around 5 years away from being able to use the discovery for a test to identify future Alzheimer's sufferers, it was a big step along the way.

The study is published in the June issue of the Archives of General Psychiatry.

Last modified on Tuesday, 06 July 2010 19:27
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