TY - JOUR
T1 - Transcriptomic and epigenomic profiling reveals altered responses to diesel emissions in Alzheimer's disease both in vitro and in population-based data
AU - Saveleva, Liudmila
AU - Cervena, Tereza
AU - Mengoni, Claudia
AU - Sima, Michal
AU - Krejcik, Zdenek
AU - Vrbova, Kristyna
AU - Sikorova, Jitka
AU - Mussalo, Laura
AU - de Crom, Tosca O. E.
AU - Simova, Zuzana
AU - Ivanova, Mariia
AU - Shahbaz, Muhammad Ali
AU - Penttila, Elina
AU - Lopponen, Heikki
AU - Koivisto, Anne M.
AU - Ikram, M. Arfan
AU - Jalava, Pasi
AU - Malm, Tarja
AU - Chew, Sweelin
AU - Vojtisek-Lom, Michal
AU - Topinka, Jan
AU - Giugno, Rosalba
AU - Rossner, Pavel
AU - Kanninen, Katja M.
N1 - Publisher Copyright:
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85206834241&partnerID=8YFLogxK
U2 - 10.1002/alz.14347
DO - 10.1002/alz.14347
M3 - Article
C2 - 39579047
SN - 1552-5260
VL - 20
SP - 8825
EP - 8843
JO - Alzheimers & Dementia
JF - Alzheimers & Dementia
IS - 12
ER -
