Authors
Yan, H., Bhat, Y., Malahov, P., Sabogal-Guaqueta, A. M., Mitchell-Garcia, T., Chen, T., Genestant, E., Ivesa, M., Nebbia, R., Gadjdjoe, P. S., Ohtonen, S., Malm, T., Guillonneau, X., Schmidt, M., Dolga, A. M.
Abstract
Alzheimer's disease (AD) is one of the most common neurodegenerative disorders, yet the environmental drivers that accelerate its progression remain poorly defined. Traffic-related air pollution is emerging as a modifiable AD risk factor, but how inhaled particles perturb microglial clearance of amyloid beta (A{beta}) is unknown. Microglia are the principal A{beta}-clearing phagocytes of the brain. Here, we showed that exposure of primary mouse microglia and human induced pluripotent stem cell-derived microglia (iMGLs) to 3-100 g/mL diesel exhaust particles (DEP) disrupted microglial homeostasis, induced morphological abnormalities, increased reactive oxygen species, impaired lysosomal degradation, and led to a concentration-dependent loss of phagocytic capacity. Importantly, DEP markedly reduces A{beta} uptake in both species. Transcriptomic profiling revealed a DEP-induced, non-canonical state characterized by metabolic reprogramming, broad suppression of inflammatory pathways, antigen-presentation, chemokine, and species-specific remodeling during subsequent A{beta} challenge, including defective chemotaxis, cell cycle, and cytoskeletal signatures. These data show that DEP profoundly alters microglial transcriptional and metabolic states, leading to impaired A{beta} clearance, which could, thereby, further contribute to AD progression.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 24 Jul 2026.
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