Air Pollution Exposure during Pregnancy and Childhood, APOE ε4 Status and Polygenic Risk Score for Alzheimer’s Disease, and Brain Structural Morphology in Preadolescents

Abstract

Background and Aim. Air pollution exposure is associated with impaired neurodevelopment, altered structural brain morphology in children and neurodegenerative disorders. Differential susceptibility to air pollution may be influenced by genetic features. We aimed to evaluate whether the apolipoprotein E (APOE) genotype or the polygenic risk score (PRS) for Alzheimer’s Disease (AD), modify the association between air pollution exposure during pregnancy and childhood and structural brain morphology in preadolescents. Methods. We included 1186 children from the Generation R Study. Concentrations of 14 air pollutants were calculated at the participants’ home address during pregnancy and childhood using land-use-regression models. Structural brain images were collected at age 9–12 years to assess (sub)cortical brain volumes. APOE status and PRS for AD were examined as effect modifiers. We conducted single-pollutant analyses with a two-way interaction between air pollution and APOE status or PRS for AD and multi-pollutant analyses with the two-way interaction. Results. Higher pregnancy PMcoarse and childhood PAHs exposure was differentially associated with larger cerebral white matter volume in APOE ε4 carriers compared to non-carriers (29485 mm3 [95% CI 6189, 52781] and 18663 mm3 [469, 36856], respectively). Higher pregnancy PMcoarse exposure was differentially associated with larger cortical grey matter volume in children with higher compared to lower PRS for AD (19436 mm3 [825, 38046]). Conclusions. APOE status and PRS for AD have a possible modifying effect on the association between air pollution exposure and brain structural morphology in preadolescents. Both seem to modify the association towards the typical development of the brain, with increasing cortical volumes, highlighting the possibility of the antagonistic pleiotropic effect (i.e., protective effect in early life but altered neurodegenerative processes in adulthood). Future studies should research this antagonistic pleiotropic effect and study trajectorial brain development using a longitudinal design. Keywords. environmental pollution, neurodevelopment, neuroimaging, genetic modifiers