Association between air pollution and CSF sTREM2 in cognitively normal older adults: The CABLE study

OBJECTIVES: Ambient air pollution aggravates the process of Alzheimer's disease (AD) pathology. Currently, the exact inflammatory mechanisms underlying these links from clinical research remain largely unclear. METHODS: This study included 1,131 cognitively intact individuals from the Chinese Alzheimer's Biomarker and LifestylE database with data provided on cerebrospinal fluid (CSF) AD biomarkers (amyloid beta‐peptide 42 [Aβ42], total tau [t‐tau], and phosphorylated tau [p‐tau]), neuroinflammatory (CSF sTREM2), and systemic inflammatory markers (high sensitivity C‐reactive protein and peripheral immune cells). The 2‐year averaged levels of ambient fine particulate matter with diameter <2.5 μm (PM(2.5)), nitrogen dioxide (NO(2)), and ozone (O(3)) were estimated at each participant's residence. Multiple‐adjusted models were approached to detect associations of air pollution with inflammatory markers and AD‐related proteins. RESULTS: Ambient 2‐year averaged exposure of PM(2.5) was associated with changes of neuroinflammatory markers, that is, CSF sTREM2 (β = −0.116, p = 0.0002). Similar results were found for O(3) exposure among the elderly (β = −0.111, p = 0.0280) or urban population (β = −0.090, p = 0.0144). No significant evidence supported NO(2) related to CSF sTREM2. For potentially causal associations with accumulated AD pathologies, the total effects of PM(2.5) on CSF amyloid‐related protein (CSF Aβ42 and p‐tau/Aβ42) were partly mediated by CSF sTREM2, with proportions of 14.22% and 47.15%, respectively. Additional analyses found inverse associations between peripheral inflammatory markers with PM(2.5) and NO(2), but a positive correlation with O(3). INTERPRETATION: These findings demonstrated a strong link between PM(2.5) exposure and microglial dysfunction. Furthermore, CSF sTREM2 as a key mediator modulated the influences of PM(2.5) exposure on AD amyloid pathologies.