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Air pollution and Alzheimer disease phenotype deplete esterified proresolving lipid mediator reserves in the brain
Ameer Y. Taha, Qing Xiang Shen, Yurika Otoki, Nuanyi Liang, Kelley T. Patten, Anthony E. Valenzuela, Christopher Wallis, Douglas J. Rowland et al.. JCI Insight, 2025-05-13
Topic: Amyloid, tau and blood-test diagnosis
BACKGROUNDTraffic-related air pollution (TRAP) is a risk factor for Alzheimer disease (AD), where unresolved brain inflammation has been linked to deficits in the levels of free lipid mediators that enable the resolution of inflammation. It is unknown whether these deficits are due to reductions in esterified lipid pools, the main source of free bioactive proresolving lipids in the brain, and whether they are related AD pathophysiology.METHODSThis unknown was tested by measuring brain esterified lipid mediators and pathogenic markers of AD in TgF344-AD and WT male and female rats exposed to filtered air or TRAP for 14 months; it was also tested in human postmortem prefrontal cortex of individuals with or without AD.RESULTSSignificant reductions in proresolving lipid mediators esterified to neutral lipids and/or phospholipids were seen in AD and TRAP-exposed female rats, where levels were associated with inflammation, synaptic loss, and impaired glucose metabolism. Lower esterified proresolving lipid mediator concentrations were associated with older age in prefrontal cortex of humans with AD compared with controls.CONCLUSIONImpaired resolution in AD is due to depletion of esterified proresolving lipid pools that supply the brain with free bioactive mediators involved in inflammation resolution. TRAP exposure alters the same esterified resolution pathways, reflecting convergent mechanisms underlying AD.
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APA 7th
Taha, A. Y., Shen, Q. X., Otoki, Y., Liang, N., Patten, K. T., Valenzuela, A. E., et al. (2025). Air pollution and Alzheimer disease phenotype deplete esterified proresolving lipid mediator reserves in the brain. JCI Insight. https://doi.org/10.1172/jci.insight.175917
Vancouver
Taha AY, Shen QX, Otoki Y, Liang N, Patten KT, Valenzuela AE, et al. Air pollution and Alzheimer disease phenotype deplete esterified proresolving lipid mediator reserves in the brain. JCI Insight. 2025. doi:10.1172/jci.insight.175917. PMID: 40359012.
BibTeX
@article{taha2025-40359012,
author = {Taha, Ameer Y. and Shen, Qing Xiang and Otoki, Yurika and Liang, Nuanyi and Patten, Kelley T. and Valenzuela, Anthony E. and Wallis, Christopher and Rowland, Douglas J. and others},
title = {{Air pollution and Alzheimer disease phenotype deplete esterified proresolving lipid mediator reserves in the brain}},
journal = {JCI Insight},
year = {2025},
doi = {10.1172/jci.insight.175917},
pmid = {40359012},
url = {https://doi.org/10.1172/jci.insight.175917}
}
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Key findings
- It is unknown whether these deficits are due to reductions in esterified lipid pools, the main source of free bioactive proresolving lipids in the brain, and whether they are related AD pathophysiology.METHODSThis unknown was tested by measuring brain esterified lipid mediators and pathogenic markers of AD in TgF344-AD and WT male and female rats exposed to filtered air or TRAP for 14 months; it was also tested in human postmortem prefrontal cortex of individuals with or without AD.RESULTSSignificant reductions in proresolving lipid mediators esterified to neutral lipids and/or phospholipids were seen in AD and TRAP-exposed female rats, where levels were associated with inflammation, synaptic loss, and impaired glucose metabolism.
- Lower esterified proresolving lipid mediator concentrations were associated with older age in prefrontal cortex of humans with AD compared with controls.CONCLUSIONImpaired resolution in AD is due to depletion of esterified proresolving lipid pools that supply the brain with free bioactive mediators involved in inflammation resolution.
Why it matters
In rats exposed to traffic-related air pollution and in human postmortem prefrontal cortex, lower levels of esterified proresolving lipid mediators were associated with inflammation, synaptic loss and impaired glucose metabolism, and with older age in people with Alzheimer's disease. This identifies a possible mechanism but does not test any treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (JCI Insight) |
| Journal's citation record | 2 / 4 | JCI Insight: journal h-index 173 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 1 / 6 | Cited 0.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Pamela J. Lein: h-index 65 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of California, Davis: institution h-index 1,257 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40359012) |
| Free to read | 2 / 2 | Free to read |
| Total | 36 / 100 | — |
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