New Risk Factor for ALS, FTD and AD.

Highlights
▪ DNA methylation
   and ALS.
▪ Heavy metals and
  oxidative stress.
▪ Link to EMF exposure.

The neurology community is always seeking to identify factors that may contribute to the initiation of neurodegenerative disease to better understand how to treat these conditions and ideally reduce the incidence.

And recent findings from a collaborative study has come to light that identifies an additional risk factor relevant to amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer’s disease (AD):
"After identifying TET2 (a gene that encodes a protein that catalyzes DNA methylation), the team looked at previously generated genetic data from more than 32,000 healthy people and people with neurodegenerative diseases. The study data confirmed that variants in TET2, in both protein-coding and non-coding regions, were more likely to be present in the genomes of people with ALS, Alzheimer’s, or FTD than in people without these diseases."  

Basically, DNA methylation is a normal mechanism used by cells to control gene expression, essentially an epigenetic signaling tool that can fix genes in the “off” position. And when something alters the process, that’s when issues (e.g. neurodegenerative disease) can arise.

BUT...here’s the bigger question - what are the environmental factors that are pulling the trigger on these mutations that could lead to a faulty TET2 protein, which then disrupts how the brain ages and contributes to the development of neurodegenerative disease? These factors are something upon which we must remain laser-focused when talking about DNA methylation.

A closer look at the environmental influences at work.

Researchers have long-studied DNA methylation and the relationship between aging and neurodegenerative diseases including ALS, AD, and FTD. Study findings indicate that alterations of methylation pathways by factors such as environmental chemicals have been implicated as risk factors. These chemicals include polychlorinated biphenyls (PCBs), lead, bisphenol A (BPA), mercury, and pesticides. You may recall that many manufacturers of plastic water and other bottles and canned foods began labeling items as “BPA-free” and in 2012 in the face of consumer pressure a law was passed forbidding its use in baby-related products.

Alteration of DNA methylation can also be initiated by:
Oxidative stress – While oxidative stress does occur naturally and contributes to the aging process, oxidative states exert a significant influence on a wide range of biological and molecular processes and functions. When their balance is shifted towards enhanced amounts of free radicals, pathological phenomena can occur, as the generation of reactive oxygen species (ROS) in tissue microenvironment or in the systemic circulation can be detrimental.  Current advances in our understanding of epigenetics have revealed a parallel scenario showing the influence of oxidative stress as a major regulator of epigenetic gene regulation via modification of DNA methylation, histones, and microRNAs.

Heavy metal exposure – in addition to mercury, other heavy metals that are “classified as human carcinogens”1 include arsenic, lead, cadmium and lead.
Unresolved past emotional trauma.
Lifestyle factors (e.g. unhealthy diet, smoking, lack of exercise, excessive alcohol consumption)
Hormones (in both women and men).
Stress – we’ve previously discussed the role of stress and glucocorticoids and the effects on the brain so be sure to read our recent blog and other related articles for further elaboration.

In the news: environmental risks and ALS.

Recent news spotlighted the results of an alarming study citing the increased risk of ALS  among those who work in agriculture and other areas that expose people to pesticides, paint solvents, electromagnetic fields (EMFs), and heavy metals. This population-based study conducted in Italy warrants larger studies to examine the findings that “working in agriculture, with its use of pesticides, increased the odds of developing ALS by 2.1 times, whereas activities in the manufacturing sector were linked with 1.48 times greater chance of ALS compared with the service sector.”

Interestingly and equally concerning is the correlation between increased risk of disease incidence and exposure to EMFs, which we know affects all of us regardless of industry, occupation, whether at home or at work. EMF exposure and the corresponding effects are not limited to only those in the agricultural sector – it is a troubling facet of the technology that literally surrounds us every day (e.g. electrical wires, cell towers, etc.) and one that we need to better understand relevant to the health implications.

In fact, in March of this year we focused on EMFs and 5G technology in our blog “What’s the big deal about 5G?” and examined some of the many studies that reveal a link to not only neurological conditions, but to other health problems as well including certain cancers (in both adults and children), cognitive decline, oxidative stress and more. Please be sure to review this article for more details as well as our suggestions for ways you can more safely continue to use your electronic devices while minimizing the potential negative impacts.

The takeaway here is not that we can attribute any one specific cause of ALS or other disorder of the brain or body. BUT…we have to consider that genetics, while a factor in neurodegenerative disease, is only a piece of the puzzle. And we must follow best-practices recommendations for a healthy lifestyle and maintain a stringent avoidance of chemicals and environmental toxins that can alter the DNA methylation process!

As always, we are here to answer your questions or provide additional explanations so please don’t hesitate to reach out.

In health and hope,
Dr. Suzanne Gazda

Additional references:

Health IT Analytics
https://healthitanalytics.com/news/researchers-identify-new-risk-factor-for-alzheimers-disease-als

HudsonAlpha Institute for Biotechnology
https://hudsonalpha.org/hudsonalpha-scientists-collaborate-to-uncover-a-gene-that-doubles-the-risk-of-developing-several-neurodegenerative-diseases/

1https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144270/