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.

Figure 1.

Map of the geographic distribution of our study population and their residential ${\mathrm{PM}}_{2.5}$ exposure concentrations in the year prior to specimen collection. Each dot represents an EHBS participant. (A) Annual ambient residential ${\mathrm{PM}}_{2.5}$ (in ${\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$) exposure by quintile ($n=\mathrm{1,113}$). (B) Annual traffic-related residential ${\mathrm{PM}}_{2.5}$ exposure (in μg/m³) by quintile ($n=\mathrm{1,080}$). Note: EHBS, Emory Healthy Brain Study; ${\mathrm{PM}}_{2.5}$, fine particulate matter.

Figure 2.

Associations between residential ${\mathrm{PM}}_{2.5}$ exposure and AD CSF biomarker concentrations. Effect Estimate ($\pm 95\%$ CI) of 1, 3, and 5-y ambient (A–E) ($n=\mathrm{1,113}$) and traffic-related (F–J) ($n=\mathrm{1,080}$) ${\mathrm{PM}}_{2.5}$ exposure on AD CSF biomarker concentrations (in pg/mL) (${\mathrm{A}\mathrm{\beta }}_{42}$, tTau, pTau, ${\text{tTau}/\mathrm{A}\mathrm{\beta }}_{42}$, and ${\text{pTau}/\mathrm{A}\mathrm{\beta }}_{42}$). All estimates are standardized and adjusted for gender, age, N-SES, race, ethnicity, educational attainment, and BMI. The dashed line indicates the significance threshold: 0 for linear regression. Numeric data can be found in Table S4. Note: ${\mathrm{A}\mathrm{\beta }}_{42}$, beta-amyloid 42; AD, Alzheimer’s disease; BMI, body mass index; CI, confidence interval; CSF, cerebrospinal fluid; N-SES, neighborhood socioeconomic status; ${\mathrm{PM}}_{2.5}$, fine particulate matter; pTau, phosphorylated Tau; tTau, total Tau.

Figure 3.

Effect modification by other common risk factors for AD. Effect ($\pm 95\%$ CI) of yearly ambient ${\mathrm{PM}}_{2.5}$ exposure on ${\mathrm{A}\mathrm{\beta }}_{42}$ CSF concentrations (in pg/mL) by (A) $\text{APOE-}\mathrm{\epsilon }4$ allele carriership, (B) AD family history, (C) ADI, (D) gender, and (E) age. Presented as overall and stratified effects for dichotomous variables and as continuous for age, with interaction $p$-values depicted on each graph. The dashed line indicates the significance threshold: 0 for linear regression. The overall effect in Figure 3A ($n=855$) differs slightly from Figure 3B–D ($n=\mathrm{1,113}$) due to the decreased sample size after including only participants with APOE genotype data. Numeric data can be found in Table S10. Note: ${\mathrm{A}\mathrm{\beta }}_{42}$, beta-amyloid 42; ADI, Area Deprivation Index $\text{APOE-}\mathrm{\epsilon }4$, apolipoprotein E4; CI, confidence interval; CSF, cerebrospinal fluid; ${\mathrm{PM}}_{2.5}$, fine particulate matter with aerodynamic diameter $\le 2.5\mathrm{\mu }\mathrm{m}$.