Air Pollution in Mexico City Has Detrimental Impact on Alzheimer’s Disease

Results from a recent study conducted by scientists at the Universidad Nacional Autónoma de México, Instituto Nacional de Pediatría, Centro Médico Cozumel Universities of Montana, Valle de México, Boise State and North Carolina, revealed that air pollution has a harmful effect on hippocampal metabolites as early neurodegeneration markers among young urbanites that carry an allele 4 of the apolipoprotein E gene (APOE). According to the study, this phenomenon is associated with an increased risk for Alzheimer’s disease (AD) and is also a marker of poor prognosis in the recovery from traumatic brain injury (TBI).

During their lifetime, children and parents living in Mexico City are exposed to air pollutants, with concentrations above the USA recommendations, including fine particulate matter (PM 2.5). In this study, researchers analysed 57 children and one parent (n=48) that shared the same APOE allele: either allele 3, 3/3, that is linked with no risk of Alzheimer’s or allele 4, 3/4 or 4/4 the least common genotype linked with risk of AD, as well as augmented levels of triglycerides, cholesterol, lipoproteins of low density and development of atherosclerosis and coronary heart disease.

The study focused on the hippocampus, a brain structure that is involved in memory processes and some affective behaviors. The researchers measured three major brain metabolites in the hippocampus with resource to a brain imaging technique known as proton magnetic resonance spectroscopy. The results revealed that the right hippocampus NAA/Cr ratio, functional integrity and reflective neuronal density, were all decreased in Mexico City APOE ε4 children when compared to children who had low pollution exposure. The left hippocampus NAA/Cr ratio of Mexico City APOE ε4 parents was found to be different than their children, with the lowest scores observed in parents.

There was a decrease in hippocampal N-acetylaspartate (NAA)/creatine(Cr), a molecule that is crucial for optimal performance of the hippocampus, found to affect APOE ε4 children as well as in their parents. The findings were concerning as this level of neurodegeneration is usually observed in AD patients, in mouse models of AD and in adults with mild cognitive impairment.

Children, teenagers and young adults from Mexico City carried key risk markers for Alzheimer’s Disease: phosphorilated tau along significant brain and intrathecal neuroinflammation, a dysregulation in immune responses, a breakdown of endothelial and epithelial barriers, damage to the neurovascular unit, and brain accumulation of metals that are related with combustion. These young subjects also presented a dysregulation in regulatory hormones feeding, olfaction deficits and defects in short-term memory and attention. Moreover, they were found to have below-average scores in the Verbal and Full Scale of the IQ in comparison to children that are less exposed to air pollution .

“APOE ε4 is likely playing a role in Mexico City children’s response to their cumulative air pollution exposures. Of importance for health and educational issues, Mexico City children’s detrimental hippocampal responses will likely have a negative impact on academic achievement and social development,” said Dr. Lilian Calderon-Garcidueas. “The effects of poverty, urban violence and air pollution-related stress on impaired cognitive skills are also very important for the developing brain and can’t be ignored.”

“These results add to growing data suggesting APOE ε4 carriers could have a higher risk of developing early AD if they reside in a polluted urban environment, and unfortunately this statement applies to individuals all around the world with high exposures to air pollutants regardless of ethnicity,” added Dr. Calderón-Garcidueas.

There could be an acceleration of neurodegenerative changes as a consequence of the combined effects of residing in a highly polluted city, APOE ε4, lower cognitive reserves, urban stress, and poor nutrition. Results from a recent study have showed a 138% increase in the risk of AD per increase of 4.34 μg/m3 in PM 2.5, indicating that a continuous exposure to PM 2.5 and to ozone above the US EPA recommendations may be linked to the risk of AD development.

A better understanding in the interactions and effects of APOE ε4 and air pollution in young people’s health could provide new insights on the prevention of AD. “We have a 50-year window of opportunity between the time urban children experience the detrimental effects we are describing here and when they will present with mild cognitive impairment and dementia. APOE ε4, the most prevalent genetic risk factor for AD, has been understudied in children and teens. Our efforts should be aimed to identify and mitigate environmental factors influencing Alzheimer’s disease and to neuroprotect high risk children. Unfortunately, to date there has been little support for studying the detrimental effects of air pollution on the pediatric brain,” the authors concluded.