CALBINDIN-D28K: A RELIABLE INDICATOR AND POSSIBLE MEDIATOR OF NEURONAL DEFICITS IN ALZHEIMER'S DISEASE

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes a relentless decline in memory and other cognitive functions. It affects nearly half of those over 85, one in ten over 65, and even a small percentage of people in their 30s and 40s. The need for drugs that prevent or reverse the progression of AD in the long term is striking.

Description: Since AD is a cognitive disorder, behavioral deficits in AD-related animal models are often regarded as the most relevant end point measures for the preclinical screening of novel drugs for this disease. However, behavioral testing is cumbersome, expensive, and time consuming. It often also gives inconsistent results when carried out in different laboratories.

Using a well-characterized AD mouse model, UC researchers have discovered a strong correlation between behavioral deficits and loss of the calcium-binding protein, Calbindin-D28K (CB) in granules of the dentate gyrus in the brain. As opposed to performing the difficult and unreliable tests that are used to determine behavioral deficits directly, it is simple to reproducibly immunostain brain sections for CB. Since CB levels accurately reflect AD-related behavioral deficits, immunostaining for CB would allow for the testing of significantly larger numbers of drugs in larger numbers of mice at greater speed and reduced cost. In addition to simply performing as an indicator, CB-related pathways might also prove to play a causal role in the development of AD-related cognitive deficits. In this case, these findings could lead to the identification of novel drug targets for the treatment of this dreaded disease.

Applications:

• CB quantitations could take the place of behavioral testing in mouse models of AD and provide a simple, quick, and economical indicator for use in preclinical screening of drugs for the treatment of AD.
• Biosensor probes could be developed for CB imaging studies to identify patients who might respond to particular forms of therapy.
• CB-related pathways could provide novel targets for the identification of new drugs for AD treatment.

Reference: 2002-372

Gladstone Contact: Caryl Cachola
Telephone: 415-734-2082

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