Traffic-Related Air Pollution, APOE ε4 Status, and Neurodevelopmental Outcomes among School Children Enrolled in the BREATHE Project (Catalonia, Spain)

Abstract

Background:Traffic-related air pollution is emerging as a risk factor for Alzheimer's disease (AD) and impaired brain development. Individual differences in vulnerability to air pollution may involve the ε4 allele of Apolipoprotein E (APOE) gene, the primary genetic risk factor for AD.Objective:We analyzed whether the association between traffic air pollution and neurodevelopmental outcomes is modified by APOE ε4 status in children.Methods:Data on parent-reported behavior problems (total difficulties scores, Strengths and Difficulties Questionnaire), teacher-reported attention-deficit hyperactivity disorder (ADHD) symptom scores, cognitive performance trajectories (computerized tests of inattentiveness and working memory repeated 2–4 times during January 2012–March 2013), and APOE genotypes were obtained for 1,667 children age 7–11 y attending 39 schools in or near Barcelona. Basal ganglia volume (putamen, caudate, and globus pallidum) was measured in 163 of the children by MRI (October 2012–April 2014.) Average annual outdoor polycyclic aromatic hydrocarbons (PAHs), elemental carbon (EC), and nitrogen dioxide (NO2) concentrations were estimated based on measurements at each school (two 1-wk campaigns conducted 6 months apart in 2012).Results:APOE ε4 allele carriers had significantly higher behavior problem scores than noncarriers, and adverse associations with PAHs and NO2 were stronger or limited to ε4 carriers for behavior problem scores (P-interaction 0.03 and 0.04), caudate volume (P-interaction 0.04 and 0.03), and inattentiveness trajectories (P-interaction 0.15 and 0.08, respectively). Patterns of associations with the same outcomes were similar for EC.Conclusion:PAHs, EC, and NO2 were associated with higher behavior problem scores, smaller reductions in inattentiveness over time, and smaller caudate volume in APOE ε4 allele carriers in our study population, and corresponding associations were weak or absent among ε4 noncarriers. These findings support a potential role of APOE in biological mechanisms that may contribute to associations between air pollution and neurobehavioral outcomes in children. https://doi.org/10.1289/EHP2246

Outdoor Air Pollution and Brain Structure and Function From Across Childhood to Young Adulthood: A Methodological Review of Brain MRI Studies

“…More recently the BREATHE project has also examined how PAHs, EC, and NO 2 relate to basal ganglia volumes using structural MRI (37, 39). A negative association was found between outdoor benzo[a]pyrene (BAP) and both the right and left caudate nucleus volumes; a similar finding was found when using a total score of outdoor PAHs (37).…”

“…Neither BAP nor total PAH levels related to the ratio of total gray and white matter to intracranial volume (i.e., overall brain size) (37). Expanding on these findings, 163 children with both MRI and genetic information were examined to determine if vulnerability to air pollution may vary by the e4 allele in the apolipoprotein E (APOE) gene – a primary genetic risk factor for Alzheimer's disease (39). Higher average annual NO 2 and PAH were again shown to relate to smaller caudate volumes from the BREATHE study, with a larger effect estimate in children carrying the APOE-e4 allele (39).…”

Beyond the looking glass: recent advances in understanding the impact of environmental exposures on neuropsychiatric disease

“…Chemical exposures-gene interactions that influence risk of psychiatric and neurologic diseases have also been reported. For example, individuals with increased air pollutant or heavy metal exposure and a particular genetic variant have increased risk of neurodevelopmental disorders compared to individuals without the genetic variant, suggesting the genetic variant makes them more susceptible to the chemical exposure [42][43][44][45][46]. Interaction between cigarette smoking and genotype at the PON1 gene locus were observed to influence the risk of bipolar and major depression disorders [47].…”

Air Pollution and Risk of Neurobehavioral Problems: Is APOE ε4 Status a Factor?

“…In the present study,4 researchers hypothesized that children’s APOE ε4 status could strengthen the relationship between TRAP exposure and negative neurodevelopmental outcomes. They used data from the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) project.…”

“…Traffic-related air pollution (TRAP) has been associated with adverse respiratory, cardiovascular, and neurological outcomes,1 , 2 , 3 associations that may be moderated by an individual’s genetic background 2. A recent report in Environmental Health Perspectives suggests that school-age children who are carriers of a genetic allele called APOE ε4 may be more susceptible to adverse neurobehavioral outcomes in association with TRAP exposures 4…”