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The bidirectional lung brain-axis of amyloid-β pathology: ozone dysregulates the peri-plaque microenvironment
Greve HJ, Dunbar AL, Lombo CG, Ahmed C, Thang M, Messenger EJ, Mumaw CL, Johnson JA et al.. Brain : a journal of neurology, 2023-03-01
Topic: Brain proteins, microglia and lab models
The mechanisms underlying how urban air pollution affects Alzheimer's disease (AD) are largely unknown. Ozone (O3) is a reactive gas component of air pollution linked to increased AD risk, but is confined to the respiratory tract after inhalation, implicating the peripheral immune response to air pollution in AD neuropathology. Here, we demonstrate that O3 exposure impaired the ability of microglia, the brain's parenchymal immune cells, to associate with and form a protective barrier around Aβ plaques, leading to augmented dystrophic neurites and increased Aβ plaque load.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Greve, H. J., Dunbar, A. L., Lombo, C. G., Ahmed, C., Thang, M., Messenger, E. J., et al. (2023). The bidirectional lung brain-axis of amyloid-β pathology: ozone dysregulates the peri-plaque microenvironment. Brain : a journal of neurology. https://doi.org/10.1093/brain/awac113
Vancouver
Greve HJ, Dunbar AL, Lombo CG, Ahmed C, Thang M, Messenger EJ, et al. The bidirectional lung brain-axis of amyloid-β pathology: ozone dysregulates the peri-plaque microenvironment. Brain : a journal of neurology. 2023. doi:10.1093/brain/awac113. PMID: 35348636.
BibTeX
@article{greve2023-35348636,
author = {Greve, H. J. and Dunbar, A. L. and Lombo, C. G. and Ahmed, C. and Thang, M. and Messenger, E. J. and Mumaw, C. L. and Johnson, J. A. and others},
title = {{The bidirectional lung brain-axis of amyloid-β pathology: ozone dysregulates the peri-plaque microenvironment}},
journal = {Brain : a journal of neurology},
year = {2023},
doi = {10.1093/brain/awac113},
pmid = {35348636},
url = {https://doi.org/10.1093/brain/awac113}
}
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Key findings
- Ozone (O3) is a reactive gas component of air pollution linked to increased AD risk, but is confined to the respiratory tract after inhalation, implicating the peripheral immune response to air pollution in AD neuropathology.
- Here, we demonstrate that O3 exposure impaired the ability of microglia, the brain's parenchymal immune cells, to associate with and form a protective barrier around Aβ plaques, leading to augmented dystrophic neurites and increased Aβ plaque load.
- Spatial proteomic profiling analysis of peri-plaque proteins revealed a microenvironment-specific signature of dysregulated disease-associated microglia protein expression and increased pathogenic molecule levels with O3 exposure.
- Unexpectedly, 5xFAD mice exhibited an augmented pulmonary cell and humoral immune response to O3, supporting that ongoing neuropathology may regulate the peripheral O3 response.
Why it matters
In this study, ozone exposure impaired microglia's ability to form a protective barrier around Aβ plaques, leading to more damaged neurites and increased plaque load. This suggests that air pollution may worsen Alzheimer's pathology through effects on the immune system, but it does not show a treatment or cure.
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Study details
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 3 / 5 | 2023 — within 6 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 79 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.8 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 3 / 6 | Cited 7.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 3 / 4 | Cited 67 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Michelle L. Block: h-index 45 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Indiana University School of Medicine: institution h-index 784 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35348636) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1093/brain/awac113
- PubMed: 35348636
- Original source →
- Free full text: IUScholarWorks (Indiana University) →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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