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

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 (PM2.5) on early predictors of future disease risk. Objectives We investigated the association between 1, 3, and 5-year exposure to ambient and traffic-related PM2.5 and cerebrospinal fluid (CSF) biomarkers of AD. Methods We conducted a cross-sectional analysis using data from 1,113 cognitively healthy adults (aged 45-75 years) from the Emory Healthy Brain Study in Georgia, USA. CSF biomarker concentrations of Aβ42, tTau, and pTau, were collected at enrollment (between 2016-2020) and analyzed with the Roche Elecsys system. Annual ambient and traffic-related residential PM2.5 concentrations were estimated at a 1km and 250m resolution, respectively, and 3- and 5-year average exposures were computed for each participant based on time of specimen collection. Associations between PM2.5 and CSF biomarker concentrations, considering continuous and dichotomous (dichotomized at clinical cut-offs for AD-biomarker positivity) 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; IQR=0.845) increases in 1-year [β: -0.101; 95%-confidence interval (CI): -0.18, -0.02] and 3-year (β: -0.078; 95%-CI: -0.15, -0.00) ambient fine PM2.5 exposures were negatively associated with Aβ42 CSF concentrations. Associations between ambient PM2.5 and Aβ42 were similar for 5-year estimates, but not significant (β: -0.076; 95%-CI: -0.160, 0.005). Dichotomized CSF variables revealed similar and significant associations between ambient PM2.5 and Aβ42. Associations with traffic-related PM2.5 were similar but not significant. PM2.5 exposures were not associated with tTau, pTau, tTau/Aβ42, or pTau/Aβ42 levels at enrollment. Conclusion In our cross-sectional study, PM2.5 exposure was associated with a significant decrease in CSF Aβ42 which suggests an accumulation of amyloid plaques in the brain and an increased risk of developing AD. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the National Institute on Aging (NIA) [R01AG070937 (Lah) and R01AG079170 (Hüls/Wingo)] and a HERCULES Pilot Project via National Institute of Environmental Health Sciences (NIEHS) P30ES019776 (Hüls). The traffic-related air pollution exposure assessment was supported by Pilot Grant via NIA P50AG025688 (Hüls/Liang) and the NIH grant R21ES032117 (Liang). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All participants completed an online consent process prior to enrollment, and the Emory University Institutional Review Board gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.