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

Abstract

AbstractIntroductionHigher fine particulate matter (PM2.5) exposure has been found to be associated with Alzheimer’s disease (AD). PM2.5has 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 PM2.5and AD. However, little prior research exisits to support these hypotheses. Therefore, this paper aims to investigate the association between traffic-related PM2.5and AD hallmark pathology, including effect modification byAPOEgenotype, in an autopsy cohort.MethodsBrain 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 PM2.5concentrations were modeled for the metro-Atlanta area during 2002-2019 with a spatial resolution of 200-250m. One-, 3-, and 5-year average PM2.5concentrations prior to death were matched to participants home address. We assessed the association between traffic-related PM2.5and AD hallmark pathology, as well as effect modification byAPOEgenotype, using adjusted ordinal logistic regression models.ResultsTraffic-related PM2.5was 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). PM2.5had harmful, but non-significant associations on Braak Stage and ABC score. The strongest associations between PM2.5and neuropathology markers were among those withoutAPOEε4alleles (e.g., for CERAD and 1-year exposure window, OR: 2.31; 95% CI: 1.36, 3.94), though interaction between PM2.5andAPOEgenotype was not statistically significant.ConclusionsOur study found traffic-related PM2.5exposure was associated with CERAD score in an autopsy cohort, contributing to epidemiologic evidence that PM2.5affects Aβ deposition in the brain. This association was particularly strong among donors withoutAPOEε4alleles. Future studies should further investigate the biological mechanisms behind this assocation.