Air pollution is associated with sex-specific longitudinal changes in astrocytic and neuroinflammatory processes linked to cognitive decline in Alzheimer's disease at-risk individuals

Alzheimers Dement. 2026 Oct;22(10):e71837. doi: 10.1002/alz.71837.

ABSTRACT

INTRODUCTION: Air pollution is associated with dementia risk, but its role during preclinical Alzheimer's disease (AD) remains unclear.

METHODS: We examined long-term residential exposure to traffic-related air pollution in 226 cognitively unimpaired middle-aged individuals at increased risk of AD from the ALzheimer's and FAmilies ALFA+ cohort (a nested longitudinal cohort within the ALzheimer's and Families parent cohort). Participants underwent baseline and 3-year follow-up cerebrospinal fluid (CSF) assessment of AD, neurodegeneration, astrocytic, microglial, and inflammatory biomarkers. Exposure to nitrogen dioxide (NO₂), particulate matter (PM)₁₀, PM_2.5, and PM_2.5 absorbance was estimated using land-use regression models. Sex-interaction and stratified analyses were performed. Mediation analyses evaluated cognitive and brain-age outcomes.

RESULTS: Sex-dependent associations were observed between air pollution exposure and CSF inflammatory and astrocytic biomarkers. Higher exposure was associated with longitudinal increases in glial fibrillary acidic protein (GFAP) and interleukin (IL) -6, primarily in women. GFAP partially mediated associations between air pollution exposure and worsening executive and attentional performance.

DISCUSSION: Findings support sex-specific astroglial and neuroinflammatory susceptibility to traffic-related air pollution in preclinical AD.

TRIAL REGISTRATION: The ALFA+ study has been registered at ClinicalTrials.gov (10-06-2015, identifier: NCT02485730).

PMID:42872554 | DOI:10.1002/alz.71837