A compelling new study is suggesting signs of the neurodegenerative disease Amyotrophic lateral sclerosis (ALS) may be detectable in teeth, decades before the onset of any symptoms. The research points to a lifelong dysfunction in metabolizing metals as a possible factor in the onset of this still mysterious disease.
ALS, also known as Lou Gehrig’s disease, is a devastating neurodegenerative disease with no known cause or cure. After Alzheimer’s and Parkinson’s, ALS is the third most common neurodegenerative disease and it usually appears around the age of 60.
The disease is generally thought to be caused by an equal balance of genetic and environmental factors. And while a number of genes have been linked to ALS, the environmental factors that may play a role are still incredibly unclear.
“Genetic studies have yielded important contributions to our understanding of ALS, but they do not tell the complete story,” explains co-investigator on the new study, Eva Feldman. “Our group has previously shown a link between persistent organic pollutants and ALS risk and progression, but there is also evidence pointing to metals as an ALS risk factor.”
A substantial volume of research has suggested a link between exposure to metals and the development of a number of neurodegenerative diseases. One hypothesis raised is that a process called metal dyshomeostasis could play a role in the early development of these diseases. A number of metals, including copper, zinc and iron, can be naturally found in the brain. However, if the body’s normal homeostatic mechanisms are not functioning correctly, elevated levels of these metals can slowly accumulate.
As our permanent adult teeth grow during adolescence, they mineralize in a way that resembles growth rings on a tree. Prior studies have found our teeth can hold stable deposits of trace metals, and studying the chronological rings in our teeth can offer insights into early-life metal uptake.
The new research conducted at Mount Sinai examined teeth taken from 36 ALS patients, either during a dental extraction or at autopsy, and compared metal uptake to 31 healthy control samples. Using a previously developed novel analysis technique the researchers were able to create temporal profiles of each subject’s environmental metal exposure during childhood, as well as calculating the person’s ability to metabolize metals.
The results clearly revealed the patients who ultimately went on to develop ALS in their older age displayed dysregulated metal uptake during their early years of life. Increased childhood uptake of 11 different metals was detected in the study, including chromium, manganese, nickel, tin, and zinc.
“This is the first study to show a clear signature at birth and within the first decade of life, well before any clinical signs or symptoms of the disease,” explains Manish Arora, senior author on the study. “We hope in the long term, after validation of this work in larger studies, that this will lead to preventive strategies. What’s exciting about this work is that we are looking at biological pathways that we could potentially modify with drug development.”
The study does cautiously note it cannot confirm a causal connection between ALS and childhood metal dyshomeostasis. However, a subsequent mouse study did offer some additional verification of the potential association between ALS and metal uptake as measured in teeth.
The general hypothesis raised by this study suggests the neurodegeneration associated with ALS could begin slowly, and decades before symptoms appear. If this association is further verified then it certainly could point researchers toward novel preventative treatments. And, it could offer the possibility of testing a child’s discarded baby teeth to detect metal uptake dysregulation as a very early risk marker for later development of neurodegenerative disease.
The new research was published in the journal Annals of Clinical and Translational Neurology.
Source: Mount Sinai
