Air pollution and plasma amyloid beta: Evidence from the Ginkgo Evaluation of Memory Study

Abstract

BACKGROUND AND AIM: Accumulation of amyloid beta (Aβ) proteins are central to the development of Alzheimer’s disease (AD). Air pollution has also been implicated in AD through its potential to cause neuroinflammation, microglia activation and white matter abnormalities. To date, few epidemiologic studies have examined the association between air pollution and Aβ. METHODS: The Ginkgo Evaluation of Memory Study (GEMS) is a longitudinal study of adults age 75 and older recruited from four US sites. Fine particulate matter (PM2.5), coarse particles (PM10) and nitrogen dioxide (NO2) were predicted from a national universal kriging model which estimated annual average pollutant levels at participant’s address one, five, 10 and 20 years prior to baseline visit. Both Aβ 1-40 and Aβ 1-42 were measured at baseline (years 2000-2002) and then again in 2008 in plasma blood samples using ELISA. After using multiple imputation by chained equations to impute missing covariates, we modelled baseline Aβ 1-40 and Aβ 1-42 separately using linear regression models and repeat measures (i.e., pooled) data using multilevel models with random intercepts. Final models were adjusted for several socio-demographic and behavioral covariates as well as cystatin C and apolipoprotein E ε4 carrier status. RESULTS:Pooled analyses included 4650 observations on 3004 participants. An interquartile range (IQR, 2-µg/m3) higher 5-year average PM2.5 was associated with a 4.9% higher Aβ 1-40 (95% CI: 3.6%, 6.3%) and a 10.9% higher Aβ 1-42 level (95% CI: 6.7%, 15.2%). A 7 ppb (one IQR) higher 5-year averaged NO2 was associated with a 10% higher Aβ 1-40 (95% CI: 7.7%, 12.4%) and 17.8% higher Aβ 1-42 level (95% CI: 10.4%, 25.7%). Similar results were seen for other pollutant-biomarker associations, although analysis of baseline Aβ data found attenuated results. CONCLUSIONS:Findings suggest a robust association between PM2.5, PM10 and NO2 and both plasma Aβ 1-40 and Aβ 1-42. KEYWORDS: air pollution, fine particulate matter, dementia, amyloid beta, Alzheimer's Disease