Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease with no cure or effective treatment. Research suggests that PM2.5 exposure may contribute to other neurodegenerative diseases such as Alzheimer’s disease, but few studies have evaluated the association between PM2.5 exposure and ALS.
Exploring Relevant Time Windows in the Association Between PM2.5 Exposure and Amyotrophic Lateral Sclerosis: A Case-Control Study in Denmark is the first study to analyze various long-term time windows of exposure to PM2.5 at the residence level and its association to ALS. This is a population-based case-control study in the Danish population spanning 1989 to 2013, with obtained patient data from the Danish National Patient Registry (DNPR). This is one of the most extensive ALS studies of environmental factors and provides a unique opportunity to evaluate the influence of time on PM2.5 exposure. We examined PM2.5 exposure one, five, and 10-years preceding the date of the first hospitalization and assessed both cumulative and delayed associations using a distributed lag model.
The study suggests exposure to PM2.5 within the five years prior to the ALS diagnosis is more relevant than exposure in earlier years. If this critical window of exposure falls within the prodromal or pre-manifest stage of ALS, which is likely, researchers hypothesize that PM2.5 exposure in these stages potentially adds to the ongoing cellular or molecular process of the disease. This hypothesis would suggest that PM2.5 exposure during the prodromal stage of the disease may contribute to a more rapid disease progression. Given that this is one of the first and few studies evaluating sensitive windows of exposure in ALS, future studies are necessary to confirm our findings and the contribution of PM2.5 exposure to ALS.
It is likely exposure to environmental stressors including PM2.5 may contribute to, or exacerbate already ongoing, neuronal degeneration in ALS patients. Inhaled PM2.5 is known to reach deep into the lungs and enter the blood circulation, subsequently triggering a cascade of events including oxidative stress and damage to the blood-brain barrier. These molecular damages may combine with ongoing cellular processes in the pre-symptomatic stages of ALS and eventually contribute to initiate clinical ALS. Examining time windows of PM2.5 exposure can provide insight into important pathological processes and improve the characterization of the PM2.5-ALS association. Furthermore, identifying the susceptible time windows of exposure to modifiable environmental factors, such as PM2.5, can open new avenues to reduce ALS’s health and financial burden.