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Normal cellular enzyme becomes marker for Alzheimer's disease

Scientists have discovered a new molecular marker for Alzheimer's disease--a normal cellular protein that piles up in nerve cells ravaged by the disease.

Alzheimer's disease (AD) is an irreversible disorder that worsens with time. As a result of damage to brain cells, AD produces its hallmark symptoms: mild forgetfulness that progresses to severe and debilitating memory loss. Except for a minority of cases (6 to 7 percent) caused by faulty genes, scientists don't yet know what causes this devastating disease that affects an estimated 4 million people in the United States.

A research team supported by the National Institutes of Health (NIH) examined the brains of people who had died from AD and found abnormally large amounts of the cellular signpost--a normal enzyme in the body called casein kinase-1 (CK-1). The researchers found that a high level of CK-1 was present in nerve cells inside cellular sacs called vacuoles. The findings indicate that a high CK-1 level in vacuoles may be a useful marker for AD, along with the two other long-recognized cellular abnormalities, or "lesions," associated with the disease: plaques and tangles.

The work appears in the October issue of the American Journal of Pathology.

Previous research had already shown that such vacuoles, called "GVD (granulovacuolar degeneration) bodies," were a prominent feature in about half of all AD cases. Scientists also already knew that the vacuoles tended to accumulate in a region of the brain called the hippocampus that is particularly vulnerable in AD, and is normally very important for learning and memory. Nonetheless, GVD bodies have remained poorly understood by scientists because they have been stubbornly difficult to locate within autopsied brain tissue. Until now, no good markers for GVD bodies were available to scientists studying AD.

The new work not only enables researchers to use CK-1 as a molecular label for studying GVD bodies, but also forges a link betwee
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Contact: Alison Davis
davisa@nigms.nih.gov
301-496-7301
NIH/National Institute of General Medical Sciences
1-Oct-1999


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