Interview with Dr. Kathrin Doppler, Department of Neurology at the University Medical School Würzburg
In patients with Parkinson's, neural cells in the brain die off that produce the neurotransmitter dopamine. Certain physical symptoms that can indicate the disease follow years later. But a reliable diagnosis can only be made through examination of the brain after the patient's death, and not during his lifetime.
MEDICA-tradefair.com talks to Dr. Kathrin Doppler of the Department of Neurology at the University Medical School Würzburg. She speaks about a method that could possibly be used to diagnose Parkinson's earlier. The examination literally only is skin-deep since it looks for proteins in the skin that are a sign of the disease.
Dr. Doppler, why is it so difficult to diagnose Parkinson's disease given the current state of medicine?
Dr. Kathrin Doppler: The symptoms are often not clear in the early stages. However, a diagnosis is primarily based on the typical clinical symptoms such as tremors, muscle rigidity or gait abnormalities. Imaging and nuclear medicine exams only provide clues for a diagnosis. A reliable diagnosis is only possible with evidence of the so-called Lewy bodies in the brain; they are deposits of the protein alpha-synuclein in nerve cells and nerve fibers. And of course, the brain is not accessible during one's lifetime.
The protein does not just deposit in the brain, but also in other regions of the body. In your study, you have researched the occurrence in the skin. What role does alpha-synuclein play in Parkinson’s disease?
Doppler: The deposit of phosphorylated alpha-synuclein is the neuropathological feature of Parkinson's disease. Previous studies were able to detect it on nerves in the gastrointestinal tract, in the salivary glands and also in small amounts in the skin. So far, it is totally unclear whether and how these deposits lead to the destruction or malfunction of nerve cells.
We were able to detect deposits of the protein in the skin during all disease stages in this study. This is why it is very important in the future to be able to also examine a larger number of people in early stages, because the protein is of particular diagnostic interest in this case.
What communalities do these affected nerve cells of brain and skin show?
Doppler: You need to differentiate between nerve cells, that being the cell bodies and their extensions, the nerve fibers. There are only nerve fibers in the skin. The cell bodies are located in the spinal ganglia, directly next to the spinal cord and send their extensions into the skin. We found the protein primarily in the nerve fibers of autonomous nerve cells. This is the part of the nervous system that cannot be consciously controlled. It controls sweat glands for instance. We know from the brain that with Parkinson’s disease areas of the autonomic nervous system are affected early on.
As another parallel, thin, unmarked nerve fibers are affected in the brain and in the skin, meaning those that do not have a myelin sheath.
What did the design of your study look like?
Doppler: The study included 31 patients with Parkinson's disease and 35 healthy subjects. We extracted skin biopsies from all participants on the lower leg, thigh, back and fingers and immunohistochemically tested for the occurrence of phosphorylated alpha-synuclein in the nerve fibers. In addition, we recorded the number of different types of nerve fiber. The study participants also underwent tests to exclude other nerve fiber damages.
And how do you intend to continue this work?
Doppler: We could analyze in a follow-up study to what extent skin biopsies are really suited to be a diagnostic tool for Parkinson’s disease. To be able to make a statement on the diagnostic value, the specificity and sensitivity of the examination need to be studied with a large number of patients. This group should incorporate all disease stages in a consistent manner. The biopsy location, the size and depth of the biopsy as well as its optimal histologic processing also has a big influence on the reliability of the diagnosis. Future studies need to develop the best possible protocol.
It would also be interesting to see whether alpha-synuclein affects the nerve fibers of the skin in their function or whether it leads to their destruction. You could study this on the skin, since it is very accessible compared to the brain.
You were able to detect the protein particularly on patients' backs. Is this connected to the nerve fibers that emanate from the spinal cord?
Doppler: Quite possibly, yes. It is peculiar that the number of nerve fibers with deposits of phosphorylated alpha-synuclein increased from the body periphery to the trunk. We know from the brain that alpha-synuclein spreads out into different areas depending on the stage. It is possible that it is similar with the body periphery. Yet it could also be related to the fact the nerve fibers are shorter in the back than those that reach all the way to the lower legs or that there is higher density of nerve fibers in the back.
What could a future diagnostic procedure look like?
Doppler: Whether the method is suitable for diagnostic purposes needs to be determined in further studies. Based on our current state of knowledge it is definitely conceivable to test skin biopsies for the occurrence of phosphorylated alpha-synuclein if Parkinson’s disease is suspected. In doing so, we could come closer to a diagnosis especially in the early stage, when a diagnosis is still uncertain based on clinical symptoms.