One of the things that makes diagnosing neurodegenerative diseases so difficult is the lack of symptoms prior to the disease progressing past the point of no return. For example, in Parkinson’s disease, only once 90% of the Substantia Nigra (an area in the brain which produces the neurotransmitter Dopamine) has been degraded does the person start producing symptoms. Symptoms with other diseases such as Alzheimer’s and Huntington’s only appear after significant damage has been done. If we were able to implement drugs such as L-Dopa, or other similar dopamine antagonists into a person with Parkinsons’ system earlier, we would be able to substantially decrease the degradation process, thus extending people’s lives significantly. What are the ways that we can do this? I was determined to find some disorders and alternative ways of diagnosis. It seems as though biomarkers seem to be the most promising way of early diagnosis.

A biomarker is a measurable indicator of a biological condition, usually a pathogen whose presence can be determined through examining one’s body fluid. Alyward indicates that a biomarker must meet three key conditions to be classified as such. 1) It must be objectively measureable; 2) it must be able to predict known endpoints; and 3) it must be associated with known mechanisms of pathology of the disease. There are many promising biomarkers for neurodegenerative diseases that we may be able to use to identify a disease at a substantially earlier stage. While these haven’t yet been implemented into current medical checks, they might be in the near future. This way, one will be able to identify how one’s biomarkers are changing over time, and hence be aware of any changes that may be indicative of disease. There are numerous other biomarkers being investigated for Alzheimer’s disease, but these two have the largest direct link to disease indication.

In an article I recently read by Aylward, both a neuroimaging technique and a biomarker for diagnosing Huntington’s disease are discussed in detail. Alyward first discusses the possibility of using MRI and striatal volume (the area degraded in Huntington’s leading to excessive movement) as a biomarker. The idea is that since an area of the brain is being degraded, you will be able to see structural changes in the brain that are only seen in patients with Huntington’s. Thus, this biomarker follows all three of Alyward’s initial conditions for a biomarker. The benefit of Huntington’s is that it does have a clear genetic link, so genetic tests can also reveal the disease. However, there are many other neurodegenerative disease, such as Alzheimer’s or Parkinson’s where the genetic link is not as clear cut.

In another article, Craig-Schapiro et al. examine some of the biomarkers for Alzheimer’s disease. There are two types proteins that accumulate in Alzheimer’s disease. The first type if Amyloid-Beta (A-B). In a normal, healthy brain, A-B proteins are removed from the brain via the cerebrospinal fluid (CSF). In Alzheimer’s, this doesn’t occur, and the A-B proteins stick together forming plaques. The second type of protein is Tau. Tau proteins in Alzheimer’s have been altered, and thus clump together forming “tangles”. When a cell dies, it releases it’s protein, which is subsequently released into the CSF. Thus, if we take a sample of the CSF and see an absence of A-B protein or an accumulation of this altered Tau protein, it indicates the possibility of Alzheimer’s disease.

One of the main problems with all of these technologies is that we can never be sure if there is a difference between the current state and the previous state without testing the person at a previous stage. Having controls tested to indicate a normal baseline is the best we currently have, but there is no way that this baseline is applicable for everyone, as everyone has a significantly different brain. If we were to test a person at certain stages of their lives to have valid comparable samples, we would increase our ability for early diagnosis much earlier. If only the cost of such technologies were such that we would be able to implement such testing earlier in life. Hopefully some type of baseline tests will be implemented in the near future to be able to capture disease earlier.

Works Cited:

Aylward, Elizabeth H. “Magnetic Resonance Imaging Striatal Volumes: A Biomarker for Clinical Trials in Huntington’s Disease.” Movement disorders : Official Journal of the Movement Disorder Society 29.11 (2014): 1429-33.

URL: http://onlinelibrary.wiley.com.ezproxy.library.ubc.ca/doi/10.1002/mds.26013/full

Craig-Schapiro, Rebecca, Anne M. Fagan, and David M. Holtzman. “Biomarkers of Alzheimer’s Disease.” Neurobiology of Disease 35.2 (2009): 128-40.

URL: http://www.sciencedirect.com.ezproxy.library.ubc.ca/science/article/pii/S0969996108002544#