Clusterin Blood Protein Linked to Development of Alzheimer’s Disease

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In new research from the UK, high levels of a blood plasma protein called clusterin have been linked to the development and severity of Alzheimer’s disease. Researchers estimate that the new finding could be used to create a range of tests to diagnose dementia patients earlier so treatments can be used to delay symptoms.

Simon Lovestone, lead researcher from the Institute of Psychiatry at King’s College London, used a technique called proteomics which analyzes proteins. They conducted two “discovery phase” studies in 95 patients and found that clusterin, a protein associated with apoptosis, or programmed cell death, was linked to early signs of Alzheimer’s disease. The protein appears to increase atrophy in the hippocampal region of the brain.

After the initial study, the researchers then evaluated clusterin levels in almost 700 people, including 464 with Alzheimer’s disease, and found a link between higher levels of the protein and severity of disease, rapid progression of the condition, and atrophy in the enthorhinal cortex, which plays a role in memory.

"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 Lovestone. "And even when they had signs of 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 the disease."

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Lovestone believes the discovery is the first step toward a preclinical or prodromal test to diagnose Alzheimer’s patients. A prodromal test is one that can detect the very early stages of disease before specific symptoms are showing.

Alzheimer's is the most common form of dementia, a brain-wasting condition that affects around 35 million people around the world. As the population ages, Alzheimer’s Disease International predicts the number of patients with Alzheimer’s will double every 20 years.

Individuals with Alzheimer's disease display several findings in their blood and cerebrospinal fluid that may reflect neuropathological changes, according to background information in the article. For example, patients with Alzheimer's disease have lower levels of amyloid-beta peptides and higher levels of total and phosphorylated tau concentration in the cerebrospinal fluid, which reflect the formation of hallmark plaques and tangles in the brain.

Despite decades of research, doctors still have few effective weapons against it. Drugs can relieve some of the symptoms temporarily, but patients gradually lose their memories, their ability to navigate and understand the world, and to care for themselves.

Lovestone said the next step to develop a better test for detection of clusterin should take about a year. "Once we've then designed the better test, we need to look at it in larger groups of people to see if our results are replicated," he said. "That whole process will take between three to five years."

Source reference:
Thambisetty M et al. "Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease" Arch Gen Psychiatry 2010; 67(7): 739-748.

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