I predict that within the next decade, blood-based biomarkers will be routinely used as screening tools to stratify risk in functionally intact older adults—by which I mean individuals in their 30s, 40s, and beyond—much like how clinical labs currently guide risk assessment for kidney or cardiovascular disease during annual check-ups. Today the diagnosis of neurodegenerative disease is heavy, almost too heavy for acceptance and implementation of screening tools. However, as therapies continue to emerge and improve, the resistance to asymptomatic diagnosis will decrease in parallel. Now, imagine a world—just around the corner—where symptoms of Lewy body disorders, including Parkinson’s disease, are preventable because we can detect pathology early, similar to how we now approach in situ cancer. The urgent question becomes: What are the early biomarkers of these diseases, and how do we develop them? What populations should we study to uncover the molecular signatures of early disease? How do we validate these markers? Should we focus on individuals who carry known genetic risk variants? Is REM sleep behavior disorder (RBD) early enough—or presymptomatic enough—to serve as a reliable window for biomarker discovery?
Hi @elahif01 , thanks for sharing your thoughts! Imagining this future world with earlier pathology detection is exciting and, as you mentioned, leads to a suite of formidable research questions which needs to be addressed. Is there a particular direction your lab’s work has prioritized as you consider all these angles?
I’m also curious if community members with interest in biomarkers (@Kimia.Abedi, @awiederhold, @ara8, @J.G, @rickhelmich), genetic data (@nisha, @sahare, @amygallagher, @mariariverapaz), or clinical data (@mengxi.yang, @dmarinme, @clinmed9, @marekpiatek) have thoughts on screening in pre-symptomatic stages of neurdegenerative diseases? How do you navigate these and similar questions in your work?
Hi @elahif01 and thank you for your interesting post! And I do like the idea that you brought that the acceptance of the use of these biomarkers at an asymptomatic disease stage will increase as treatments become more often. As a clinician, I always had the problem of fitting the advances in the field in the patients contexts of actively seeking a diagnosis for a condition that he doesn’t present yet. This is something quite simple that I have never given thought before!
However, I do think that your prediction of this happening in the next decade to be partially correct. I say that because I believe that the first disease-modifying treatments to be available for such neurodegenerative diseases will come from the genetic part, especially the monogenic patients, so I think that these biomarkers (or genetic tests, in this specific case) will be more accepted by the public in that specific situation within these 10 years, and not for all all cases of a specific condition (such as PD or Alzheimer’s). But of course I do think other treatments that are more general to these neurodegenerative diseases will follow in the following decades and that, therefore, general biomarkers for these conditions will gain more acceptance!
I do think that RBD is a very interesting biomarker, however, as it is nonspecific regarding which synucleinopathy it is associated with, I think it will have a lesser impact, because it is very broad and I think that it will be difficult that we identify a treatment that could deal with PD, MSA and Lewy Body Dementia.
I agree with genetics first insight. Thanks for your input!
Re: RBD and general application to all subtypes of synucleinolapathy—it may be useful for early risk stratification (screening) and additional tests would determine subtype. But also we may have subtype-agnostic treatment options, that target more general principles in neurodegenerative disease conditions such as neuro vascular decoupling, energetic failure, ox stress etc.
Yes we are very actively working on development of biomarker panels (proteomic signatures) that help break up heterogenous cohorts into biological subtypes and ultimately improve therapeutics but also improve predictive models that are important for drug discovery and clinical care both—this is a huge unmet need. The new molecular tools have increased reliability of omic measurements and thereby provide an opportunity for development of better biomarkers.
Ah, I agree with you regarding RBD being useful for early risk stratification and additional tests helping us determine the subtype. That makes total sense and is very efficient. Nice touch!
And regarding the investigation of biomarker panels for the sporadic disease, I also do agree with you! I think that these panels will be very useful for us in identifying treatments. I can envision ourselves dealing with PD and other neurodegenerative diseases the same way as we currently deal with a lot of cancers: we identify the pathways that are most affected and provide treatments targeting those specific pathways! So identifying these panels is the necessary first step to arrive at this!