Biomarkers of neurodegenerative diseases (ND)
Neurodegenerative diseases, such as Multiple Sclerosis (MS), Parkinson Disease (PD), Alzheimer’s Disease (AD), and Amyotrophic Lateral Sclerosis (ALS), directly affect over 6.5 million Americans per year and cost more than $252 billion per year (nearly 1.5% of the USA GDP).
Despite the heavy human and fiscal toll these taken by diseases, no cures exist and molecular tests for disease diagnosis or prognosis are lacking. [MS has the oligoclonal banding test that is used as part of diagnosis, but it is often run incorrectly or interpreted poorly.] Evidence suggests that chronic neurological diseases may all be triggered or hastened by inflammatory mechanisms. GWAS studies in AD and PD have implicated several genes that encode HLA and other inflammatory mediators. Similarly in MS, immunologically relevant genes are significantly overrepresented among those mapping to loci identified in GWAS studies.
In order to better understand the acute biomarkers of disease onset and progression, Orion Bionetworks set out to compile a reference list of fluid-based biomarkers across these four neurodegenerative diseases. We primarily relied on reviews and meta-analyses to guide us to the primary research papers that explored the levels of biomarkers in bio-fluids of human patients. This overview list was made possible through the following well-researched reviews:
- Comabella, Manuel, and Xavier Montalban. “Body fluid biomarkers in multiple sclerosis.” The Lancet Neurology1 (2014): 113-126.
- Graber, Jerome J., and Suhayl Dhib-Jalbut. “Biomarkers of disease activity in multiple sclerosis.” Journal of the neurological sciences1 (2011): 1-10.
- Katsavos, Serafeim, and Maria Anagnostouli. “Biomarkers in multiple sclerosis: an up-to-date overview.” Multiple sclerosis international 2013 (2013).
- Parnetti, Lucilla, et al. “Cerebrospinal fluid biomarkers in Parkinson disease.” Nature Reviews Neurology3 (2013): 131-140.
- Robelin, Laura, and Jose Luis Gonzalez De Aguilar. “Blood Biomarkers for Amyotrophic Lateral Sclerosis: Myth or Reality?.” BioMed Research International 2014 (2014).
We are providing the list to the research community as a service, recognizing that this list is not exhaustive, and would appreciate your feedback and identification of important missing markers and evidence.
Figure 1: A Cytoscape [http://www.cytoscape.org/] visualization of the biomarkers and their associated diseases reveals limited overlap between biomarkers under exploration across the neurodegenerative diseases of interest. Octagons are the disease hubs and purple ellipses represent biomarkers of study. The connecting lines represent that a particular biomarker has been studied in a particular disease, and line thickness indicates the number of studies for a particular biomarker-disease pair. The thicker the connecting line, the more studies that have looked at that particular relationship. AD: Alzheimer’s Disease; ALS: Amyotrophic Lateral Sclerosis; MS: Multiple Sclerosis; NMO: Neuromyelitis Optica; PD: Parkson’s Disease.
Table 1: Biomarkers of Neurodegeneration
We sampled both cross-sectional studies, which reveal biomarkers useful for diagnosis, and longitudinal studies that shed light on prognostic biomarkers indicative of disease progression. To better understand the power of each study listed, we captured the study size, whether neurodegenerative controls were used, the type of assay, the type of biomarker, and the direction of change revealed in the study. You will notice that some studies show conflicting results in the direction of change.
We are happy to share this Cross Disease Biomarkers Spreadsheet. Please contact us for a copy.
Note: To view the Biomarkers lists (part 1 and part 2) below, click the image below; a new window will open. Click on the image in the new window to view it at full size.