Prions Require High-Tech Hunting
News From The Frontier

by Sandra J. Ackerman

March, 2005

When mad cow disease and its human equivalent, Creutzfeldt-Jakob disease (CJD), were traced in 1997 to an infectious particle called a prion, the discovery brought neurologist and biochemist Stanley Prusiner a Nobel Prize. The next step seemed clear: find a way to detect disease-bearing prions in brain tissue.

Zeroing in on abnormal prions in living brain tissue has proved very difficult, however. The two techniques most commonly used—immunohistochemistry and microscopic examination of the tissue—are moderately sensitive, but they cannot detect abnormal prions at low levels. Indeed, up to now a definitive diagnosis of prion disease in an animal or human patient has been available only after autopsy.

An article in the March 1 Proceedings of the National Academy of Sciences describes an advance in this field that may allow the diagnosis of prion disease in brain biopsies from living patients. Neurologist Jiri Safar of the UCSF Institute for Neurodegenerative Diseases (which Prusiner directs), and his collaborators call their technique the CDI, or conformation-dependent immunoassay. The great sensitivity of the CDI comes from the application of a new type of antibody that can recognize abnormal prions in a tissue sample by their distinct molecular shape.