Greater exposure to nitrogen dioxide linked to higher levels of biomarkers of Alzheimer's disease in the brain

Investigators from the Barcelonaβeta Brain Research Center (BBRC), the research arm of the Pasqual Maragall Foundation, in collaboration with ISGlobal, have found an association between exposure to air pollution and higher levels of biomarkers of Alzheimer’s disease, particularly in individuals with elevated beta-amyloid deposition in the brain. The results of the study, which was supported by the ”la Caixa” Foundation, have been published in Environment International.

“In line with those of other recent studies, our findings indicate that the tiny suspended particles and gases in air pollution, produced primarily by road traffic, may be an environmental risk factor for Alzheimer’s disease”,  highlights Dr. Marta Crous Bou, one of the authors of the study and a scientific collaborator with the BBRC. She goes on to say that the study “provides evidence that air pollution may have a particular effect on individuals who already have disease biomarkers, in this case, beta-amyloid deposition in the brain, and that exposure may contribute to the advance or progression of the disease.”

The results of this study indicate that greater exposure to nitrogen dioxide and to suspended particles with a diameter of 2.5 microns or less (PM_2.5) is associated with higher levels of beta-amyloid protein deposition in the brain, a biological alteration that occurs in Alzheimer’s disease. On the other hand, exposures containing PM₁₀ (particles with a diameter of 10 microns or less) and PM_2.5 particles were associated with higher levels of neurofilament light (NfL) in cerebrospinal fluid, a biomarker of neuronal injury. The study findings also suggest that the effect of air pollutant exposure on NfL levels was stronger in individuals who carry the ε4 variant of the APOE gene, the main risk-factor gene for Alzheimer’s disease.

These findings are consistent with hypotheses which propose that fine particles such as PM_2.5 can cross the blood-brain barrier and reach the brain. Air pollution is also one of the most prevalent sources of environmentally-induced inflammation and oxidative stress, two factors involved in neurodegenerative processes.

New Horizons

Although the mechanisms involved in these associations are still poorly understood, the findings of this study reinforce the emerging scientific evidence that air pollution may be a risk factor in the development of Alzheimer’s disease. “It is important to emphasize that this is a modifiable factor, and one to which a large part of the population is exposed. Even though the associated risks are small, a reduction in exposure would lead to a decrease in the morbidity associated with this disease,” explains ISGlobal researcher Dr. Silvia Alemany, first author of the study. “Future studies will allow us to demonstrate whether its effects are related to disease progression.”   

Dr. Natàlia Vilor-Tejedor, co-author of the study and a member of the BBRC’s Neuroimaging Research Group, emphasises that the discoveries “will make it possible for us to analyse the effects of air pollution on the brain and cognition, while taking into account the role played by genes”. She goes on to explain that the results “also open the door to the investigation of the long-term impact of pollution on mechanisms involved in Alzheimer’s disease and to research outside of the city of Barcelona and in a broader segment of the population.”

The participants were selected from the ALFA + study. The sample included 156 cognitively unimpaired adults with a mean age of 57 years, many of them relatives of patients with Alzheimer’s disease. The researchers only included individuals who had lived in the city of Barcelona at the same address for at least the preceding 3 years and for whom reliable geocoded data was available.

Reference

Silvia Alemany*, Marta Crous-Bou*, Natalia Vilor-Tejedor, Marta Milà-Alomà, Marc Suárez-Calvet, Gemma Salvadó, Marta Cirach, Eider M. Arenaza-Urquijo, Gonzalo Sanchez-Benavides, Oriol Grau-Rivera, Carolina Minguillon, Karine Fauria, Gwendlyn Kollmorgen, Juan Domingo Gispert, Mireia Gascón, Mark Nieuwenhuijsen, Henrik Zetterberg, Kaj Blennow, Jordi Sunyer, José Luis Molinuevo, Associations between air pollution and biomarkers of Alzheimer’s disease in cognitively unimpaired individuals, Environment International, Volume 157, 2021, 106864, ISSN 0160-4120, https://doi.org/10.1016/j.envint.2021.106864.