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Semaglutide ameliorates neuroinflammation and cognitive impairment in APP/PS1 mice
Yuan Y, Zhang J, Zhang Z, Zhai Y, Cheng XJ, Xue L, Zhao F, Cao L et al.. Molecular and cellular biochemistry, 2026-05-13
Topic: Brain proteins, microglia and lab models
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown neuroprotective potential, but the mechanisms underlying these effects remain incompletely understood. This study investigated whether semaglutide, a long-acting GLP-1RA, ameliorates AD-like phenotypes in APP/PS1 mice and explored associated changes in neuroinflammatory signaling and blood-brain barrier (BBB) integrity. Eight-month-old amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice were treated with semaglutide for 8 weeks. Cognitive performance was evaluated using the Morris water maze (MWM). AD-related neuropathology, neuroinflammation-associated protein markers, BBB integrity-related measures, and microglial ultrastructure were assessed using histological, ultrastructural, and molecular approaches. Fecal microbiota composition was profiled by 16 S rRNA amplicon sequencing. Semaglutide improved cognitive performance in APP/PS1 mice and was associated with attenuation of neuronal loss-related changes, reduced Aβ deposition, and improved synaptic ultrastructure. Semaglutide also reduced the AD-associated upregulation of inflammasome-/pyroptosis-associated proteins (including NLRP3-related and caspase-11-related markers) and TLR4/NF-κB-related inflammatory signaling proteins, accompanied by attenuation of microglial mitochondrial ultrastructural abnormalities. In addition, semaglutide improved markers of BBB integrity (tight junction proteins and brain albumin levels) and increased BBB-related Aβ clearance proteins (LRP-1 and P-gp). Gut microbiota profiling revealed genus-level differences between WT and APP/PS1 mice without significant changes in α- or β-diversity. Semaglutide was associated with improved cognition and attenuation of AD-like pathology and neuroinflammatory signaling in APP/PS1 mice, accompanied by partial preservation of BBB integrity.
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APA 7th
Yuan, Y., Zhang, J., Zhang, Z., Zhai, Y., Cheng, X. J., Xue, L., et al. (2026). Semaglutide ameliorates neuroinflammation and cognitive impairment in APP/PS1 mice. Molecular and cellular biochemistry. https://doi.org/10.1007/s11010-026-05568-0
Vancouver
Yuan Y, Zhang J, Zhang Z, Zhai Y, Cheng XJ, Xue L, et al. Semaglutide ameliorates neuroinflammation and cognitive impairment in APP/PS1 mice. Molecular and cellular biochemistry. 2026. doi:10.1007/s11010-026-05568-0. PMID: 42126676.
BibTeX
@article{yuan2026-42126676,
author = {Yuan, Y. and Zhang, J. and Zhang, Z. and Zhai, Y. and Cheng, X. J. and Xue, L. and Zhao, F. and Cao, L. and others},
title = {{Semaglutide ameliorates neuroinflammation and cognitive impairment in APP/PS1 mice}},
journal = {Molecular and cellular biochemistry},
year = {2026},
doi = {10.1007/s11010-026-05568-0},
pmid = {42126676},
url = {https://doi.org/10.1007/s11010-026-05568-0}
}
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Key findings
- Semaglutide improved cognitive performance in APP/PS1 mice and was associated with attenuation of neuronal loss-related changes, reduced Aβ deposition, and improved synaptic ultrastructure.
- Gut microbiota profiling revealed genus-level differences between WT and APP/PS1 mice without significant changes in α- or β-diversity.
- Semaglutide was associated with improved cognition and attenuation of AD-like pathology and neuroinflammatory signaling in APP/PS1 mice, accompanied by partial preservation of BBB integrity.
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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 randomized / 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 and multicenter collaboration, so those were left out: it earned 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular and cellular biochemistry) |
| 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 | 5 / 5 | 2026 — within 1 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 |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42126676) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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