Air pollution and biomarkers of Alzheimer's disease in cognitively unimpaired individuals

Background Air quality might contribute to incidence of dementia-related disorders, including Alzheimer’s disease (AD). The aim of our study was to examine whether air pollution may be associated with abnormal concentrations of AD cerebrospinal fluid (CSF) and neuroimaging biomarkers in cognitively unimpaired individuals at increased risk of AD. Additionally, potential effect modification by amyloid-β(Aβ) and APOE-ɛ4 status was investigated. Methods The ALFA (ALzheimer and FAmilies) study is a prospective cohort of cognitively unimpaired, middle-aged subjects, many AD patients’ offspring. Land Use Regression models were used to estimate residential exposure to air pollutants including nitrogen oxides (NO2, NOx) and particulate matter (PM2.5, PM2.5 abs, PM10, PM coarse). For a subset, we measured CSF levels of Aβ42, Aβ40, p-tau, t-tau and neurofilament light (NfL) using NeuroToolKit and Elecsys® immunoassays (Roche Diagnostics). They also underwent a [18F]flutemetamol amyloid PET scan to assess cerebral amyloid load (Centiloid). A total of 148 participants (all residents of Barcelona) with data available on exposure to air pollutants and core AD biomarkers were included in this cross-sectional analysis. Multiple linear regression models were used to test the association between exposure to air pollutants and biomarkers. Age, sex, years of education and APOE-ɛ4 status were included as potential confounders. To test for effect modification, Aβ positivity was defined by an Aβ42/Aβ40 ratio<0.071. Stratified analyses by APOE genotype were also performed. Results Greater exposure to air pollutants was associated with increased levels of CSF p-tau, t-tau and NfL, and reduced Aβ42/40 ratio. Additionally, higher exposure to nitrogen oxides was significantly associated with increased Aβ deposition in the brain (Figure1;*p<0.05). Such associations were driven by Aβ-negative individuals (p-interaction<0.05) (Figure 2;*p<0.05). Furthermore, the association between increased exposure to air pollutants and Ab deposition was only seen in APOE-ɛ4 non-carriers, while the positive association between exposure to air pollutants and CSF p-tau, t-tau and NfL was only observed among APOE-ɛ4 carriers (Figure 3;*p