Induction 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 Aβ generation. In contrast, WS produced a distinct transcriptional signature and failed to induce ferroptotic priming or lipid peroxidation, consistent with its low metal composition. Together, these findings implicate metals as a shared driver linking diverse AirP exposures to amyloidogenic vulnerability and elevated AD risk.
Authors
- Masako Morishita
- Wendy Jean Mack (ORCID: https://orcid.org/0000-0002-2474-7921)
- Henry Jay Forman (ORCID: https://orcid.org/0000-0001-5838-2791)
- Alexandra N. Demetriou (ORCID: https://orcid.org/0000-0002-9002-3593)
- Marc Vermulst (ORCID: https://orcid.org/0000-0003-4909-5496)
- M. W. Cohen
- Manuel Morales (ORCID: https://orcid.org/0000-0001-7940-8743)
- Russell E. Jacobs (ORCID: https://orcid.org/0000-0002-1382-8486)
- Mohammad Mahdi Badami (ORCID: https://orcid.org/0000-0002-0821-7453)
- Hyoungjin Park (ORCID: https://orcid.org/0009-0009-8526-9335)
- José A. Godoy-Lugo (ORCID: https://orcid.org/0000-0003-4671-3201)
- Matthew J. Campen (ORCID: https://orcid.org/0000-0002-2292-5050)
- Selena Chen (ORCID: https://orcid.org/0000-0001-5147-9507)
- Caleb Andrew Franklin
- Constantinos Sioutas
- Bérénice Anath Benayoun (ORCID: https://orcid.org/0000-0002-7401-4777)
- Caleb E. Finch (ORCID: https://orcid.org/0000-0002-7617-3958)
- Naomi Sta. Maria
- Max A. Thorwald
- Kristina Shkirkova (ORCID: https://orcid.org/0000-0002-9288-4258)
- Ararat Chakhoyan (ORCID: https://orcid.org/0000-0001-9447-495X)
- Lifu Zhao
- William J Mack
- Sindhu Daggupati
- Angela Tang-Tan
- Salma Durra
- Herbert Anson
- Skyye Dodds-Lewis
- Isabella Bent
- Claire Chung
- Giovanni Chahine
- Jean-Francois Gout
- Yashar Aghaei
Institutions
- Grand Rapids Community College (US)
- University of Southern California (US)
- University of New Mexico (US)
- New York University (US)
- Michigan State University (US)
- Mississippi State University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-01-07
- DOI
- https://doi.org/10.64898/2026.01.06.696601
- Citations
- 1
- Primary Topic
- Air Quality and Health Impacts
- Type
- article
- Field-Weighted Citation Impact
- 31.09