EAN 2023 | Unraveling subtypes of Parkinson’s disease: a focus on biomarkers
Carlo Colosimo, MD, FEAN, Santa Maria University Hospital, Terni, Italy, discusses the evolution in understanding neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. Historically, these conditions were seen as singular entities, but recent perspectives highlight the existence of distinct subtypes based on age at onset, rate of progression, and associated comorbidities. The emphasis now is on the discovery of reliable biomarkers, not just for diagnosis but for patient stratification. In the field of Parkinson’s disease, the search centers around detecting alpha-synuclein pathology in tissues other than the brain. Techniques being explored include examining cerebrospinal fluid (CSF), skin biopsies, saliva, and the olfactory mucosa to detect abnormal alpha-synuclein accumulations. Hopefully, these methods will pave the way for more personalized therapeutic approaches for patients with Parkinson’s. This interview took place at the European Academy of Neurology (EAN) 2023 Congress in Budapest, Hungary.
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Transcript (edited for clarity)
In the past we were used to put under the same umbrella people with specific degenerative disorders, like people with Parkinson disease or people with Alzheimer’s disease having just a single disorder. But it’s becoming clear over time that this is a very simplistic way to look at these common disorders. And because of the different age at onset, because of the different rate of progression, because the rate of different association of comorbidities, there are really very different subtypes of these disorders...
In the past we were used to put under the same umbrella people with specific degenerative disorders, like people with Parkinson disease or people with Alzheimer’s disease having just a single disorder. But it’s becoming clear over time that this is a very simplistic way to look at these common disorders. And because of the different age at onset, because of the different rate of progression, because the rate of different association of comorbidities, there are really very different subtypes of these disorders. Obviously, at the moment this is based mainly on the clinical features. So, let’s say there’s somebody with early onset PD, we already know from the beginning that they will be very different from somebody with very late onset PD, or somebody with prominent tremor will be different from somebody with less tremor or no tremor.
What we really need are good biomarkers, any type of biomarkers, going from wet biomarkers to neuroimaging, able to not only tell us that the specific patient has got Parkinson disease, to confirm our clinical suspicion, but also to try to stratify people. So, people having a more benign course or less benign course, people who together with the motor disorders will have dementia or behavioral disorders, people who will never develop dementia or behavioral disorders. I think this is very important, and this search for good and reliable biomarkers is really one of the key topics now in Parkinson disease research.
Probably the emerging ones are biomarkers looking at the possibility to detect alpha synuclein pathology in other tissues different from the brain, because in order to see it in the brain, you should make a brain biopsy, which is obviously quite difficult. So, there are many studies now looking at the CSF and how alpha synuclein is modified in the CSF and becoming pathological in people with PD. Many studies looking at skin biopsy, which is really almost non-invasive technique, taking a little bit of a fragment of skin and then looking at the possibility to have in the skin nerve terminals the accumulation of alpha synuclein or also in other in other fluids, like for instance in the saliva.
And recently there has been also several groups around the world looking at the possibility to have like a biopsy of olfactory mucosa, which is a tissue very closely related to central nervous system tissue where you can detect alpha synuclein pathology. So many groups are actively looking at different possible sites of detecting alpha synuclein pathology outside the central nervous system.
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