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Diagnosis of prions in patients should utilize novel strategy, team says

A technique for detecting prions in tissue, developed in recent years by UCSF scientists, is significantly more sensitive than the diagnostic procedures currently used to detect the lethal particles in samples of brain tissue from patients, according to a study performed by a UCSF team.

The finding indicates that the diagnostic technique, known as the conformation-dependent immunoassay (CDI), should be established as the standard approach for brain biopsies of patients suspected of having the disease, they say. The team is exploring whether the CDI might be adapted to detect prions in blood and muscle.

The finding suggests that reliance on the current methods for detecting prions in human brain tissue -- microscopic examination of tissue for the telltale vacuoles that form in brain cells and immunohistochemistry (IHC), which involves detecting prions in brain sections using prion protein-specific antibodies -- may have led to an under diagnosis of the disease in patients in recent years, they say. (A definitive diagnosis of the disease in humans is made only on autopsy, when a neuropathologist can analyze multiple brain regions for vacuoles and evidence of prions by IHC, and it is estimated that only 50 percent of human cases are autopsied, in part because many pathologists do not want to risk infection during the autopsy.)

In the study, the team compared the ability of the CDI and the two traditional diagnostic techniques to detect prions in various brain samples from 28 patients diagnosed on autopsy as having one of several human forms of the disease -- sporadic, familial or iatrogenic Creutzfeldt-Jakob disease (CJD). While the CDI detected the biochemical signal for prions in 100 percent of the samples studied, the traditional tests failed to detect the prion in a high proportion of cases. For example, in an experiment that focused on 18 brain regions from eight patients with sporadic CJD, the CDI detected prions in 100 percent of the samp
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
21-Feb-2005


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