biostudies-literatureUnknownShkirkova KNIA NIH HHSAir pollution (AirP) exposure is associated with increased Alzheimer's disease (AD) risk, yet AirP is chemically heterogeneous, complicating identification of shared pathogenic drivers. We examined acute cortical responses to two metal-rich AirP sources, diesel exhaust particles (DEP) and World Trade Center (WTC) dust, and compared them to woodsmoke (WS), a particulate exposure with low metal content. DEP and WTC elicited highly convergent transcriptional responses, sharing over 1200 differentially expressed genes linked to inflammation, ferroptosis, neuronal remodeling, and amyloid processing. These changes were accompanied by impaired antioxidant activity and increased lipid peroxidation within lipid rafts, a membrane microdomain critical for amyloid processing, resulting in increased AβbioRxiv : the preprint server for biology2026.01.06.696601https://www.ebi.ac.uk/biostudies/studies/S-EPMC12803064biostudies-literatureInduction of ferroptotic and amyloidogenic signatures linked to Alzheimer's disease by chemically distinct air pollutants.PMC12803064RF1 AG051521P01 AG055367Franklin CGodoy-Lugo JADurra SChahine GAghaei YZhao LDemetriou AMorales MBadami MMChakhoyan AShkirkova KJacobs REForman HJTang-Tan AChen SPark HMaria NSSThorwald MADodds-Lewis SVermulst MFinch CEDaggupati SMorishita MCohen MDBent IChung CBenayoun BACampen MSioutas CMack WJAnson HGout JFfalseInduction of ferroptotic and amyloidogenic signatures linked to Alzheimer's disease by chemically distinct air pollutants.Air pollution (AirP) exposure is associated with increased Alzheimer's disease (AD) risk, yet AirP is chemically heterogeneous, complicating identification of shared pathogenic drivers. We examined acute cortical responses to two metal-rich AirP sources, diesel exhaust particles (DEP) and World Trade Center (WTC) dust, and compared them to woodsmoke (WS), a particulate exposure with low metal content. DEP and WTC elicited highly convergent transcriptional responses, sharing over 1200 differentially expressed genes linked to inflammation, ferroptosis, neuronal remodeling, and amyloid processing. These changes were accompanied by impaired antioxidant activity and increased lipid peroxidation within lipid rafts, a membrane microdomain critical for amyloid processing, resulting in increased Aβ2026-01-01T00:00:00Z2026 Jan2026-06-04T03:14:04.496Z2026-06-04T03:10:00.68ZS-EPMC128030644154250410.64898/2026.01.06.696601