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Normal cellular enzyme becomes marker for Alzheimer's disease

n GVD bodies and the more commonly studied plaques and tangles typical of AD brains.

"The most important conclusion from our work is the existence of a molecular connection between the different lesions of Alzheimer's disease," said Dr. Jeffrey Kuret of Ohio State University and senior author of the new study. Other team members were from Northwestern University Medical Center and Rush Presbyterian Medical Center (both in Chicago), and ICOS Corporation (in Bothell, Washington).

Dr. Kuret made the recent discovery while investigating the workings and whereabouts of the CK-1 enzyme, a protein called a kinase that adds molecular tags called phosphate groups to a host of cellular components. The researchers had a suspicion that CK-1 might add phosphate tags to a protein called "tau," which is present in AD plaques, tangles, and GVD bodies. Normally, tau's job is to assemble proteins called microtubules--the cell's structural scaffolding apparatus--that stretch from one end of a nerve cell to the other to ferry nutrients and structural components. Tau gets into trouble and cannot keep its proper structure, scientists believe, when it acquires too many phosphate tags.

Putting his suspicions to the test, Dr. Kuret searched for CK-1 in the brain tissue of people who had died from AD.

The hunch proved correct: Dr. Kuret and his team turned up a 30-fold increase of one particular form of CK-1 inside GVD bodies within the hippocampus region of AD brains. This is the largest preponderance of a kinase yet discovered in AD brain tissue. The results tantalizingly suggest that CK-1 might play a role in setting the stage for, or in accelerating, the brain cell death associated with AD. However, firm proof of this idea awaits a much more detailed study of GVD bodies and their role in AD and other similar neurodegenerative diseases.

Although Dr. Kuret's work began as a basic study probing how a fundamental enzyme helps the cellular skeleton assemble, it now
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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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