A recent study contradicts much of how we believed prion diseases to affect the brain. Previously, it was believed that infectious brain proteins called PrP accumulate slowly, with one protein causing other proteins to misshapen and become dysfunctional. As the healthy copies of the protein become the diseased form, PrP, the toxic levels would increase and additionally lead to deterioration and death of brain cells. Amyloid plaques are a common result of prion diseases.
However the recent study showed that infectious proteins that lead to prion diseases seem to build up in the brain and plateau before “initiating the cascade of deterioration that leads to dementia and death.” Prions quickly build up in the brains of the mice in the first month or two and peak at about 100 million infectious particles per brain. This number can remain constant for months without any symptoms of disease.
The study was performed under the impression that if researches increased the number of the normal PrP protein in the mice brains, the number of infectious particles would also increase, meaning more normal PrP protein would eventually lead to more diseased form PrP. However, the prion levels reached a plateau after a certain point.
It was found that the the length of incubation period between initial infection and onset of disease varied with differeing levels of PrP in the brain. The onset of disease was more rapid in the mice that had more PrP in their brains. This suggests that how fast the animal gets sick is dependent upon how much PrP in general is in the brain.
This time difference between plateau of prions and disease suggests that the infection is a sepeartae process from toxicity. There may be an unstudied molecular or cellular process that converts infectious prions to toxic disease causing prions. However, this is simply an initial suggestion and there may be many other causes that have not been proposed.
Additionally, the size of the prions may be a limiting factor of toxicity of prions. The filaments of the prion protein continue to grow in the cell, and they may need to reach a certain size to become toxic. Either way, it is shown that prions do not directly kill brain cells as once expected.
If these other factors that influence toxicity can be understood, researchers may be able to incorporate various treatments to prevent the prion diseases from affecting the brain.
Prion diseases are particularly interesting, after having studied them briefly in our class Environmental Change and Emerging Infectious Disease. Kuru is an example of the intersection between disease, culture, and environment to show the complex problems that emerging infectious diseases create. I also, helped teach middle school kids about prion disease for a medical robotics challenge through First Lego League, and it was super fun! The kids learned the basics of the disease via mad cow disease, but with such an unexplored topic, much of the knowledge we currently have may be altered, as proven by this recent study.