The abnormal clumping and accumulation of alpha synuclein has been shown to cause and spread dysfunction in cells, leading some to characterize Parkinson disease by proteinopathy or as a protein disease.
The abnormal clumping and accumulation of alpha synuclein, a protein suggested to have a central role in the pathogenesis of Parkinson disease (PD), has been shown to cause and spread dysfunction in cells, leading some to characterize PD by proteinopathy or as a protein disease, said Nicki Niemann, MD, neurologist at the Muhammad Ali Parkinson Center and an assistant professor of neurology at Barrow Neurological Institute.
AJMC®: Hello, I'm Matthew Gavidia. Today on the MJH Life Sciences’ Medical World News, The American Journal of Managed Care® is pleased to welcome Dr Nicki Niemann, neurologist at the Muhammad Ali Parkinson Center and an assistant professor of neurology at Barrow Neurological Institute. Dr Niemann additionally served as a co-author of a review article titled “Parkinson Disease and Skin.”
Alpha synuclein, an abnormal protein suggested to have a central role in the pathogenesis of parkinson disease, has been found to be present in the peripheral tissue, notably the skin. Can you discuss the mechanisms behind this protein and the diagnostic role this may have in parkinson disease?
Dr Niemann: So, alpha synuclein, I'm sure most are familiar with this protein. It's a normal protein we all have, it's expressed primarily in nerve cells. It's localized in presynaptic terminals and in nuclei, and that's how it derives its name, synuclein, from synapse and nucleus.
We don't necessarily have all the pieces or all the information about how this protein works, but there's a preponderance of evidence that suggests and shows that it has an important function in several functions like vesicular trafficking, docking and priming and fusing vesicles, your transmitter release, and also how the axon functions.
In Parkinson disease, what can happen is that the protein can change conformation and kind of clump together. It can also become phosphorylated, which is also an abnormal process. The clumping together and accumulation of this protein causes problems in the machinery of the cell, and causes dysfunction and spreads to other cells. And so, by many, Parkinson disease, has been described as a proteinopathy or protein disease.
We know that people with Parkinson disease have these abnormal aggregates of alpha synuclein in the brain, but we also know that the protein can be found in other tissues. So, those other tissues would be actually many different things like the eye, the salivary glands, the adrenal glands, the heart, intestine, and indeed the skin. The interesting part about the skin is that skin is so accessible, and you can do a biopsy with minimal risk; it's very easy to do, minimal training is required, and it's usually really well tolerated by patients.
So, in the past 10 years primarily, but in the past 2 decades really, there's been a number of studies that have looked at the diagnostic utility of doing a skin biopsy. So, most of the studies that have been published suggest that skin biopsy, when done to assess for the presence of this abnormal protein, has a specificity of close to 100% and a sensitivity that, unfortunately, varies greatly from from the 20s up to the 90s.
So, I think that means that the test is very helpful when it's positive, because it helps rule the disorder in, but it may not be as helpful when it's negative because the false-negative result might or might not be a false-negative result. But in terms of clinical practice in skin biopsy, I think we're still early. It's not widely available, it is not widely used. There's still debate about what technique should be used. Should it be immunohistochemistry, as has been used up to now, or should it be more advanced or newer types of diagnostic tests, such as RT-QuIC, which has recently been the subject of a couple of studies in Parkinson disease and skin.
There's also a question about what site is best to biopsy, how big should the biopsy be, how should the biopsy be processed, and how do we standardize these things between laboratories. So, currently it’s still in early use in Parkinson disease, and I think we need a little bit more data before it can be recommended as a routine diagnostic test. But it certainly is very promising and it's very encouraging, because a big problem in Parkinson disease has been that the diagnostic accuracy, at least early on, can be somewhat suboptimal.