Many different molecules in our bodies are proteins, and they have to be correctly made and folded for the body to function properly. The accumulation of aberrant, misfolded proteins is a known feature of several different kinds of brain diseases. For example, the buildup of a protein called α-synuclein has been linked to dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and Parkinson's disease (PD). Now researchers have learned more about how one protein can be associated with these very different disorders.
"Previously, it was a mystery why one and the same protein caused three different brain diseases," said study author Dr. Anke Van der Perren of the Laboratory for Neurobiology and Gene Therapy at KU Leuven. "Now, for the first time, we've been able to identify different shapes of α-synuclein protein deposits in patients. Depending on the shape, a different disorder and, thus, a different clinical picture occurs."
In this study, an international team of researchers was able to use samples of brain tissue that were from deceased DLB, MSA, and PD patients. The scientists extracted the α-synuclein protein from these samples. Using a special technique created for this research, they copied those proteins exactly to generate more to use experimentally; then they analyzed them and exposed lab animals to these proteins.
In MSA and Parkinson's, the scientists found that the protein took on a helical shape. In the case of DLB, the protein had a cylindrical shape. The MSA protein also caused a faster and more aggressive disease, while the symptoms linked to the DLB version of the protein were milder.
Parkinson's disease tends to impact dopamine-producing neurons, and usually affects people over the age of 60. It's estimated that two percent of people older than 60 have the disorder. The second most common type of dementia is dementia with Lewy bodies, which affects around 0.4 percent of people over 65. Multiple system atrophy is a more rare disorder and is an extremely aggressive disease that has no treatment. It can cause different health problems, including pain, low blood pressure, and bladder problems. Most patients die of the disease within ten years of diagnosis.
This work may help improve diagnostics and create treatment options.
"To this day, it's very difficult to diagnose these three brain disorders. We want to further unravel the complex process of the protein deposits to gain a better understanding of how the diseases develop. In time, we hope that we'll be able to detect these harmful protein shapes and that a specific treatment can be found to slow down or even stop the disease process," said study author Professor Veerle Baekelandt of the Laboratory for Neurobiology and Gene Therapy at KU Leuven.