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

ensitivity of the CDI suggests that CDI-like tests could also prove useful for diagnosing other neurodegenerative diseases, such as Alzheimer's disease, Parkinsons's disease and fronto-temporal dementias, all of which, like prion diseases, involve various forms of protein misprocessing. These diseases currently are diagnosed by neuropathological analysis and immunohistochemistry.

"Whether immunohistochemistry underestimates the incidence of one or more of these common neurodegenerative diseases is unknown, but the CDI could shed light on these diseases," says co-author Bruce Miller, MD, UCSF A.W. and Mary Margaret Clausen Distinguished Professor of Neurology and director of the UCSF Memory and Aging Center.

The finding will be printed on-line and in print on March 1, 2005 in Proceedings of the National Academy of Sciences.

The study brings into high relief the different detection strategies of immunohistochemistry and the CDI, both of which involve revealing the presence of prions, known as PrPsc, by applying antibodies to brain tissue.

Standard immunohistochemistry, developed in the DeArmond lab 20 years ago, involves using an enzyme known as a protease, or a combination of harsh acid and high temperature treatment, to destroy normal prion protein (PrPC), which is ubiquitous in brain tissue. Once this occurs, scientists apply fluorescently lit antibodies that react with residues of the relatively resistant abnormal prion protein (PrPSc), thereby highlighting it.

The limitation of this technique is that scientists have since learned that there is a large part of the abnormal prion protein that is protease sensitive, and that portion escapes detection by the standard technique. Thus, this traditional method underestimates the level of PrPSc in tissue.

The CDI addresses this limitation by revealing the region of PrPSc that is exposed in the normal PrPC but is buried in infectious PrPSc, using high affinity, newly

Contact: Jennifer O'Brien
University of California - San Francisco

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