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.