Infectious proteins that cause brain-wasting conditions like mad cow disease appear to build up in the brain long before initiating the cascade of deterioration that leads to dementia and death, a new study of mice finds.
The findings suggest that other factors besides the misshapen infectious proteins characteristic of prion diseases may control the lethality of the disease. If scientists can determine what those factors are, future treatments may be able to prevent the infectious protein diseases — which include mad cow disease, scrapie in sheep and Creutzfeldt-Jakob disease in people — from progressing to a fatal stage.
“We don’t know what’s going on here, but we do know there’s something interesting,” says John Collinge, director of the United Kingdom Medical Research Council Prion Unit in London, who headed the new study.
Findings reported by Collinge and his colleagues in the Feb. 24 Nature contradict the idea that infectious versions of a normal brain protein called PrP accumulate slowly, gradually twisting all of the healthy copies of the protein into a disease-causing form. Researchers have thought that the disease-causing prions slowly build up to toxic levels that spell the death of brain cells.
But the new study shows that the process is anything but gradual, and that infection and toxicity are independent stages of the disease. Prions quickly build up in the brains of mice over the course of a month or two, Collinge and his colleagues found, peaking at about 100 million infectious particles per brain.
That level remains constant for months with no evidence of disease.
“Whatever you do, it sort of stops at that level and remains there for the duration of the infection,” says Collinge.
