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

Abstract

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 (PM2.5), nitrogen dioxide (NO2), and ozone (O3) 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 PM2.5 was associated with changes of neuroinflammatory markers, that is, CSF sTREM2 (β = −0.116, p = 0.0002). Similar results were found for O3 exposure among the elderly (β = −0.111, p = 0.0280) or urban population (β = −0.090, p = 0.0144). No significant evidence supported NO2 related to CSF sTREM2. For potentially causal associations with accumulated AD pathologies, the total effects of PM2.5 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 PM2.5 and NO2, but a positive correlation with O3. Interpretation These findings demonstrated a strong link between PM2.5 exposure and microglial dysfunction. Furthermore, CSF sTREM2 as a key mediator modulated the influences of PM2.5 exposure on AD amyloid pathologies.

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

“… 16 Their estimates were similarly negative but did not reach significance, likely owing to the relatively small sample size ( ). 16 Another study 15 found a statistically significant total effect of ambient on CSF as well as concentrations among cognitively healthy older individuals, which was further mediated by a CSF biomarker of neuroinflammation, sTREM2. 15 …”

“…So far, two epidemiological studies have reported associations between and CSF in cognitively healthy individuals whereas no relationships with tTau or pTau have been noted. 15 , 16 However, there are several limitations with these prior studies, including a ) the exposure assessments in Alemany et al. 16 and Li et al.…”

“… 16 and Li et al. 15 only focused on 1- or 2-y average prior to the biomarker assessment; b ) the relatively small sample size ( ) in Alemany et al., 16 and c ) the outcome assessment in Li et al., 15 which relied on the Innotest-AMYLOID(1-42) ELISA assay, an unstandardized manual method, showing a high correlation with the automated Elecsys method but higher intra- and interlaboratory variations. 17 , 18 …”

Investigating the Potential Impact of Air Pollution on Alzheimer’s Disease and the Utility of Multidimensional Imaging for Early Detection

“…By focusing on sTREM2, researchers hope to lessen the burden of amyloid buildup, delay the beginning of AD, and halt the spread of the disease. 54 Significant progress has been made in understanding complex disease mechanisms and exploring multidimensional approaches for imaging and treatment. One study utilized a multimodal approach, using deep learning to combine imaging, electronic health records (EHR), and genomic single nucleotide polymorphism data (stacked denoising autoencoders), to predict Alzheimer's disease stages and successfully classify patients into control, mild cognitive impairment, and Alzheimer's disease groups, surpassing single-modality deep learning models.…”

“…As a crucial mediator, cerebralspinal fluid (CSF) sTREM2 established a clear connection between PM2.5 exposure and microglial dysfunction by controlling the effects of PM2.5 exposure on AD amyloid pathology. By focusing on sTREM2, researchers hope to lessen the burden of amyloid buildup, delay the beginning of AD, and halt the spread of the disease …”