Chesebro mentions two theories as to why the transgenic mice did not show symptoms of illness despite being infected:
* The host cell might require the GPI anchor to receive the "toxic signal" from the abnormal prion protein
* The plaques might be less toxic than the non-plaque form of prion protein clumps
In either case, more time might be required to produce disease due to the reduced toxicity, Dr. Chesebro says.
"There was so much about this research that surprised us and gave us ideas to pursue," says Dr. Chesebro. "First, the mice didn't get sick. That's very significant. Second, the dense accumulations of scrapie plaque in the brain resembled the plaque seen in Alzheimer's, but it wasn't toxic," which might support more recent concepts about plaque in Alzheimer's patients. "Previously, most researchers thought plaques were the toxic component of Alzheimer's that kills neurons, and many treatments focus on removing the plaques. But what if the plaques are inert, as they were in this research? What if only small clumps are toxic?"
If this hypothesis proves correct, Dr. Chesebro says, the ongoing research could eventually alter scientists' views on preventing prion diseases, shifting emphasis away from stopping the production of prion protein clumps and toward preventing interactions with prion protein anchored to cells, or learning to direct abnormal prion protein accumulations to specific parts of the brain where they will not produce symptoms.
"Abnormal prion protein by itself may not be rapidly lethal--in these mice it wasn't," Dr. Chesebro says.