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MDS 2021 | Biofluid and genetic biomarkers for Parkinson’s disease

Chin-Hsien Lin, MD, PhD, National Taiwan University, Taipei, Taiwan, gives an overview of the latest advances and ongoing investigations into biomarkers to diagnose and guide the management of Parkinson’s disease (PD). Markers developed to date, predominantly clinical and neuroimaging markers, are limited in their specificity and sensitivity when applied individually. Biofluid and genetic markers appear most promising and have the potential to act objectively to facilitate early diagnosis, detect or predict disease progression, and guide clinical management. Dr Lin highlights specific α-synuclein species in the blood and LRRK2 kinase activity as promising biomarkers under investigation. This interview took place during the 2021 International Congress of Parkinson’s Disease and Movement Disorders.

Transcript (edited for clarity)

This is a very big question because the so-called biomarkers should have a specific definition, so we usually call it that could be objectively measured. So that is biological markers. So for example, if we can objectively measure a specific protein that can be detected in our biofluids or a specific kind of imaging changes that can found in a specific subgroup of patients, then we can define them as a kind of biomarkers...

This is a very big question because the so-called biomarkers should have a specific definition, so we usually call it that could be objectively measured. So that is biological markers. So for example, if we can objectively measure a specific protein that can be detected in our biofluids or a specific kind of imaging changes that can found in a specific subgroup of patients, then we can define them as a kind of biomarkers. So, it should be measured in different countries and regions. However, currently, the biofluid markers usually will be changing because the measured platforms are different.

So in this MDS Congress speech, I’m going to talk about the neuroimaging biomarkers, the biofluid biomarkers, and the clinical subtypes as markers and finally the genetic markers. So after my review and my personal point of view I think, generally speaking, the genetic markers will be much more objective compared to other biomarkers. So I will be focused on genetic biomarkers because it will link to different disease phenotypes under the big umbrella of Parkinson’s disease. And then we’ll reach to, we call it a precision medicine for a specific patient carrying specific mutations.

Actually, there are a lot about imaging biomarkers and in this talk—actually before me, there’s a very famous English United Kingdom speaker. She will talk beautifully about the clinical subtypes of Parkinson’s disease. And for imaging biomarkers, there are many new kinds of neuroimaging tools, including the structural brain MRI or molecular imaging PET scans that can help us to define whether there are specific pathological protein depositions in the human brains. For example, the amyloid-PET or tau-PET, because these kinds of specific proteins can help us to define whether they are Alzheimer’s disease-related pathology in Parkinson’s disease; because we know that for those with Parkinson’s disease dementia, they will combine or mix with this kind of Alzheimer pathology. However, the drawback is we don’t have the alpha-synuclein PET yet because alpha-synuclein is still the pathological hallmark of Parkinson’s disease.

So in my talk, I think in the most updated parts will be the biofluid and genetic markers. And for the biofluid markers, we are no longer measure the total protein of the alpha-synuclein, we can measure the specific oligomeric form or specific phosphorylated form of alpha-synuclein. And we can also measure the specific kinase activity of LRRK2 protein, because LRRK2 is an important genetic receptor for Parkinson’s disease. So again, that will link with genetic markers and biofluid markers together so if we find a patient who carries the LRRK2 mutation, and he/she also has the increase LRRK2 kinase activity from the peripheral blood cells assessed by this LRRK2 kinase activity assay, then we can try to use LRRK2 kinase inhibitors in this specific group of PD patients. So then we reach to the following precision medicines after my talk. That will be the topic of my talk.

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