Fine particulate air pollution and neuropathology markers of Alzheimer’s disease in donors with and without APOE ε4 alleles – results from an autopsy cohort

INTRODUCTION: Higher fine particulate matter (PM(2.5)) exposure has been found to be associated with Alzheimer’s disease (AD). PM(2.5) has been hypothesized to cause inflammation and oxidative stress in the brain, contributing to neuropathology. A major genetic risk factor of AD, the apolipoprotein E (APOE) gene, has also been hypothesized to modify the association between PM(2.5) and AD. However, little prior research exisits to support these hypotheses. Therefore, this paper aims to investigate the association between traffic-related PM(2.5) and AD hallmark pathology, including effect modification by APOE genotype, in an autopsy cohort. METHODS: Brain tissue donors enrolled in the Emory Goizueta Alzheimer’s Disease Research Center (ADRC) who died before 2020 (n=224) were assessed for AD pathology including Braak Stage, Consortium to Establish a Registry for AD (CERAD) score, and the combined AD neuropathologic change (ABC score). Traffic-related PM(2.5) concentrations were modeled for the metro-Atlanta area during 2002–2019 with a spatial resolution of 200–250m. One-, 3-, and 5-year average PM(2.5) concentrations prior to death were matched to participants home address. We assessed the association between traffic-related PM(2.5) and AD hallmark pathology, as well as effect modification by APOE genotype, using adjusted ordinal logistic regression models. RESULTS: Traffic-related PM(2.5) was significantly associated with CERAD score for the 1-year exposure window (OR: 1.92; 95% CI: 1.12, 3.30), and the 3-year exposure window (OR: 1.87; 95%-CI: 1.01, 3.17). PM(2.5) had harmful, but non-significant associations on Braak Stage and ABC score. The strongest associations between PM(2.5) and neuropathology markers were among those without APOE ε4 alleles (e.g., for CERAD and 1-year exposure window, OR: 2.31; 95% CI: 1.36, 3.94), though interaction between PM(2.5) and APOE genotype was not statistically significant. CONCLUSIONS: Our study found traffic-related PM(2.5) exposure was associated with CERAD score in an autopsy cohort, contributing to epidemiologic evidence that PM(2.5) affects Aβ deposition in the brain. This association was particularly strong among donors without APOE ε4 alleles. Future studies should further investigate the biological mechanisms behind this assocation.