Prion-Like Proteins Attributed To Development of Alzheimer’s Disease and Others
The most recent theory about disorders which attack the brain and spinal column received significant support this week from scientists at Washington University School of Medicine in St. Louis.
The theory proposes that these disorders should be attributed to proteins that behave like prions, which are essentially copies of normal proteins that have been corrupted in ways that cause diseases. Scientists previously believed only one particular protein could be corrupted in such a way, but the research from the lab of Marc Diamond, MD, indicates that a protein linked to Alzheimer’s disease, along with other neurodegenerative conditions, also behave very similarly to prions.
Diamond’s lab found that tau proteins could be corrupted in various ways, and that these different forms of corruption (referred to as strains) were linked to distinct and identifiable forms of damage to the brain.
“If we think of these different tau strains as different pathogens, then we can begin to describe many human disorders linked to tau based on the strains that underlie them,” said senior author Diamond, the David Clayson Professor of Neurology. “This may mean that certain antibodies or drugs, for example, will work better against certain disorders than others.”
The study was published online May 22 in Neuron, and was led by co-first authors David Sanders and Sarah Kaufman, both of whom are graduate students.
Prions consist of normal proteins that have been folded into abnormal shapes which cause the non-living proteins to behave similar to infectious microbes. The unusual shape allows the prions to replicate themselves in abnormal ways, and when the prion interacts with other normal versions of the same protein it can cause these proteins to also become prions.
“When we infected a cell with one of these misshapen copies of tau and allowed the cell to reproduce, the daughter cells contained copies of tau misfolded in the same fashion as the parent cell,” Diamond said. “Further, if we extracted the tau from an affected cell, we could reintroduce it to a naïve cell, where it would recreate the same aggregate shape. This proves that each of these differently shaped copies of the tau protein can form stable prion strains, like a virus or a bacteria, that can be passed on indefinitely.”
When Diamond used the tau prions made in cells to infect mouse brains, it showed that differently shaped strains cause different levels of brain damage. He isolated the prions from the mice, grew them in cell culture, and then infected other mice. Throughout the transfers, each particular prion strain continued to be misfolded in the same shape and to cause the same type of damage.
“Each disease had a unique tau prion strain or combination of strains associated with it,” he said. “For example, we isolated the same tau prion strain from nearly every patient with Alzheimer’s disease we examined.”