Increased levels of Aβ40 in plasma is associated with severity of exposure to airborne pollutants at the World Trade Center: A cross-sectional study of neurological biomarkers.

World Trade Center (WTC) responders who were more severely exposed to the airborne pollution while working in rescue and recovery work would have heightened circulating levels of β-Amyloid (Aβ) levels in plasma. Plasma for 905 World Trade Center (WTC) responders was retrieved in 2019 and flash frozen and assayed using single molecule analysis to measure circulating levels of two subtypes of Aβ (Aβ40, Aβ42), alongside phosphorylated tau-181, glial fibrillary acidic protein, and neurofilament-light. Plasma data were linked to demographics, blood volume, apolipoprotein-ε4 status, and medical outcomes as well as, in a subsample, with neuroimaging-based measures of cortical thickness. Amyloidogenesis was measured using the ratio of observed/expected levels of Aβ40 and labeled Normalized Aβ40. Spearman's rho was used to examine correlations; generalized linear modeling was used to examine multivariable-adjusted associations. The average age of World Trade Center (WTC) responders was 55.98 years, and 73.9% had completed at least some college. Observed Aβ40 levels were 24.61% higher than expected values, and lower in minimally exposed WTC responders as compared to severely exposed WTC responders (17.26 versus 44.48%, P = 0.005). Results remained statistically significant upon adjusting for covariates (adjusted blood volume ratio = 1.11 [1.02-1.22] p = 0.019). Normalized Aβ40 levels were associated with higher measures of phosphorylated tau-181, Aβ42, glial fibrillary acidic protein, and neurofilament-light in serology as well as, in a subsample (n = 70), with reduced cortical thickness (rho = -0.29, p = 0.020). Increased amyloidogenesis may be a neuropathological response in people who are severely and chronically exposed to neurotoxic air pollutants.