The neurotoxicity of air pollution is undefined for sex and alleles. These major risk factors of Alzheimer's disease (AD) were examined in mice given chronic exposure to nPM, a nano-sized subfraction of urban air pollution. In the cerebral cortex, female mice had two-fold more genes responding to nPM than males. Transcriptomic responses to nPM had sex- interactions in AD-relevant pathways. Only 3 mice responded to nPM in genes related to Abeta deposition and clearance (, , ). Other responding genes included axonal guidance, inflammation (AMPK, NFKB, APK/JNK signaling), and antioxidant signaling (NRF2, HIF1A). Genes downstream of NFKB and NRF2 responded in opposite directions to nPM. knockdown in microglia augmented NFKB responses to nPM, suggesting a critical role of NRF2 in air pollution neurotoxicity. These findings give a rationale for epidemiologic studies of air pollution to consider sex interactions with alleles and other AD-risk genes.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314548PMC
http://dx.doi.org/10.7554/eLife.54822DOI Listing

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