Abstract
INTRODUCTION
Studies have correlated living close to major roads with Alzheimer’s disease (AD) risk. However, the mechanisms responsible for this link remain unclear.
METHODS
We exposed olfactory mucosa (OM) cells of healthy individuals and AD patients to diesel emissions (DE). Cytotoxicity of exposure was assessed, mRNA, miRNA expression, and DNA methylation analyses were performed. The discovered altered pathways were validated using data from the human population-based Rotterdam Study.
RESULTS
DE exposure resulted in an almost four-fold higher response in AD OM cells, indicating increased susceptibility to DE effects. Methylation analysis detected different DNA methylation patterns, revealing new exposure targets. Findings were validated by analyzing data from the Rotterdam Study cohort and demonstrated a key role of nuclear factor erythroid 2–related factor 2 signaling in responses to air pollutants.
DISCUSSION
This study identifies air pollution exposure biomarkers and pinpoints key pathways activated by exposure. The data suggest that AD individuals may face heightened risks due to impaired cellular defenses.
Highlights
Healthy and AD olfactory cells respond differently to DE exposure.
AD cells are highly susceptible to DE exposure.
The NRF2 oxidative stress response is highly activated upon air pollution exposure.
DE-exposed AD cells activate the unfolded protein response pathway.
Key findings are also confirmed in a population-based study.
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This post is Copyright: Liudmila Saveleva,
Tereza Cervena,
Claudia Mengoni,
Michal Sima,
Zdenek Krejcik,
Kristyna Vrbova,
Jitka Sikorova,
Laura Mussalo,
Tosca O. E. de Crom,
Zuzana Šímová,
Mariia Ivanova,
Muhammad Ali Shahbaz,
Elina Penttilä,
Heikki Löppönen,
Anne M. Koivisto,
M. Arfan Ikram,
Pasi I Jalava,
Tarja Malm,
Sweelin Chew,
Michal Vojtisek‐Lom,
Jan Topinka,
Rosalba Giugno,
Pavel Rössner,
Katja M. Kanninen | November 23, 2024