Association between Fine Particulate Matter Exposure and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease among a Cognitively Healthy Population-Based Cohort

Abstract

Background: Epidemiological evidence suggests air pollution adversely affects cognition and increases the risk of Alzheimer's disease (AD), but little is known about the biological effects of fine particulate matter (${\mathrm{PM}}_{2.5}$, particulate matter with aerodynamic diameter $\le 2.5\mu m$) on early predictors of future disease risk.

Objectives: We investigated the association between 1-, 3-, and 5-y exposure to ambient and traffic-related ${\mathrm{PM}}_{2.5}$ and cerebrospinal fluid (CSF) biomarkers of AD.

Methods: We conducted a cross-sectional analysis using data from 1,113 cognitively healthy adults (45-75 y of age) from the Emory Healthy Brain Study in Georgia in the United States. CSF biomarker concentrations of ${A\beta }_{42}$, tTau, and pTau, were collected at enrollment (2016-2020) and analyzed with the Roche Elecsys system. Annual ambient and traffic-related residential ${\mathrm{PM}}_{2.5}$ concentrations were estimated at a $1\text{-km}$ and $250\text{-m}$ resolution, respectively, and computed for each participant's geocoded address, using three exposure time periods based on specimen collection date. Associations between ${\mathrm{PM}}_{2.5}$ and CSF biomarker concentrations, considering continuous and dichotomous (dichotomized at clinical cutoffs) outcomes, were estimated with multiple linear/logistic regression, respectively, controlling for potential confounders (age, gender, race, ethnicity, body mass index, and neighborhood socioeconomic status).

Results: Interquartile range (IQR; $\text{IQR}=0.845$) increases in 1-y [$\beta :-0.101$; 95% confidence interval (CI): $-0.18$, $-0.02$] and 3-y ($\beta :-0.078$; 95% CI: $-0.15$, $-0.00$) ambient ${\mathrm{PM}}_{2.5}$ exposures were negatively associated with ${A\beta }_{42}$ CSF concentrations. Associations between ambient ${\mathrm{PM}}_{2.5}$ and ${A\beta }_{42}$ were similar for 5-y estimates ($\beta :-0.076$; 95% CI: $-0.160$, 0.005). Dichotomized CSF variables revealed similar associations between ambient ${\mathrm{PM}}_{2.5}$ and ${A\beta }_{42}$. Associations with traffic-related ${\mathrm{PM}}_{2.5}$ were similar but not significant. Associations between ${\mathrm{PM}}_{2.5}$ exposures and tTau, pTau ${\text{tTau}/A\beta }_{42}$, or ${\text{pTau}/A\beta }_{42}$ levels were mainly null.

Conclusion: In our study, consistent trends were found between 1-y ${\mathrm{PM}}_{2.5}$ exposure and decreased CSF ${A\beta }_{42}$, which suggests an accumulation of amyloid plaques in the brain and an increased risk of developing AD. https://doi.org/10.1289/EHP13503.