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PM2.5 exposure exacerbates Alzheimer's disease pathology through lysosomal dysfunction in APP/PS1 mice
Min Wei, Wenjing Li, Guangming Bao, Zhaofei Yang, Song Li, Weidong Le. Ecotoxicology and environmental safety, 2025-08-26
Topic: Air pollution and environmental exposures
Ambient fine particulate matter (PM2.5) is a key environmental risk factor closely associated with Alzheimer's disease (AD), although its specific molecular mechanisms remain incompletely elucidated. In this study, APP/PS1 double transgenic AD mice and their wild-type (WT) littermates were used as research subjects. A chronic exposure model was established via nasal instillation of PM2.5 for 90 consecutive days to systematically investigate the effects of PM2.5 on the pathological progression of AD. Behavioral assessments demonstrated that chronic PM2.5 exposure significantly induced cognitive impairment in WT mice and exacerbated cognitive deficits in AD model mice, suggesting that PM2.5 has universal neurotoxicity. Pathological analyses further revealed that PM2.5 exposure exacerbated neuropathological changes in AD mice, manifested as significantly increased β-amyloid (Aβ) plaque deposition and enhanced tau protein hyperphosphorylation. Mechanistic investigations identified PM2.5-induced lysosomal dysfunction as a critical factor that led to dysregulation of Aβ-metabolizing proteins (e.g., PS1), thereby disrupting normal Aβ metabolism and exacerbating Aβ pathology. Concurrently, lysosomal dysfunction activated microglia, triggering neuroinflammatory responses and inducing myelin sheath damage in the hippocampus and cortex, which further disrupted the homeostasis of the neural microenvironment and aggravated Aβ pathology. In summary, this study confirms that PM2.5 exposure accelerates AD pathological progression through the synergy of multiple pathways, including lysosomal dysfunction, PS1 upregulation, neuroinflammation, and myelin damage, with lysosomal dysfunction playing a core driving role. These findings not only provide new insights into the association between PM2.5 and AD but also lay a crucial theoretical foundation for the development of targeted preventive and therapeutic strategies for AD.
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APA 7th
Wei, M., Li, W., Bao, G., Yang, Z., Li, S., & Le, W. (2025). PM2.5 exposure exacerbates Alzheimer's disease pathology through lysosomal dysfunction in APP/PS1 mice. Ecotoxicology and environmental safety. https://doi.org/10.1016/j.ecoenv.2025.118918
Vancouver
Wei M, Li W, Bao G, Yang Z, Li S, Le W. PM2.5 exposure exacerbates Alzheimer's disease pathology through lysosomal dysfunction in APP/PS1 mice. Ecotoxicology and environmental safety. 2025. doi:10.1016/j.ecoenv.2025.118918. PMID: 40865239.
BibTeX
@article{wei2025-40865239,
author = {Wei, Min and Li, Wenjing and Bao, Guangming and Yang, Zhaofei and Li, Song and Le, Weidong},
title = {{PM2.5 exposure exacerbates Alzheimer's disease pathology through lysosomal dysfunction in APP/PS1 mice}},
journal = {Ecotoxicology and environmental safety},
year = {2025},
doi = {10.1016/j.ecoenv.2025.118918},
pmid = {40865239},
url = {https://doi.org/10.1016/j.ecoenv.2025.118918}
}
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Key findings
- Ambient fine particulate matter (PM2.5) is a key environmental risk factor closely associated with Alzheimer's disease (AD), although its specific molecular mechanisms remain incompletely elucidated.
- Behavioral assessments demonstrated that chronic PM2.5 exposure significantly induced cognitive impairment in WT mice and exacerbated cognitive deficits in AD model mice, suggesting that PM2.5 has universal neurotoxicity.
- Pathological analyses further revealed that PM2.5 exposure exacerbated neuropathological changes in AD mice, manifested as significantly increased β-amyloid (Aβ) plaque deposition and enhanced tau protein hyperphosphorylation.
- These findings not only provide new insights into the association between PM2.5 and AD but also lay a crucial theoretical foundation for the development of targeted preventive and therapeutic strategies for AD.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Ecotoxicology and environmental safety) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | Laboratory or animal study (title names “app/ps1”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40865239) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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