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A novel Dual GLP-1/CCK Receptor Agonist Improves Cognitive Performance and Synaptogenesis in the 5 × FAD Alzheimer Mouse Model
Ma H, Chang Z, Sun H, Ma D, Li Z, Hao L, Zhang Z, Hölscher C et al.. Molecular neurobiology, 2025-05-08
Topic: Brain proteins, microglia and lab models
Glucagon-like peptide 1 (GLP-1) is a peptide hormone and growth factor. Cholecystokinin (CCK) is another peptide hormone, growth factor and neurotransmitter. Both peptide hormones have shown good neuroprotective effects in animal models of Alzheimer's disease (AD). In this study, we tested the effects of a dual GLP-1/CCK (25 nmol/kg ip. for 14 days) receptor agonist that had previously shown good effects in animal models of diabetes. The GLP-1 analogue Liraglutide (50 nmol/kg ip.) was used as a positive control. Memory was improved in the water maze and the Y-maze, spontaneous activity was increased, the chronic inflammation response had been reduced and levels of NLRP3, IL-10 and TNFα were brought back to physiological levels. Levels of amyloid aggregates in the brain were reduced by the drugs. The expression of proteins SIRPα and CD47 which is related to reduced inflammation levels was reduced. Importantly, growth factor signalling was much improved and growth levels of BDNF, TrkB receptor, p-CREB, and an upregulation of the PI3K-AKT signalling pathway had been observed. Post-synaptic density protein (PSD) and synaptophysin levels were reduced, too. In transmission electron microscope analysis, the synaptic cleft was found to be wider in 5xFAD mice. In Golgi stain evaluations, synapse numbers were brought back to normal levels by the drugs. In a direct comparison with Liraglutide, the dual GLP-1/CCK receptor agonist was superior in the water maze tests and in the upregulation of BDNF and TrkB levels in the brain. In other parameters, the dual agonist and Liraglutide showed comparable effects. In conclusion, the combination of GLP-1 and CCK receptor activation did not show overall improvements over single GLP-1 receptor activation.
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APA 7th
Ma, H., Chang, Z., Sun, H., Ma, D., Li, Z., Hao, L., et al. (2025). A novel Dual GLP-1/CCK Receptor Agonist Improves Cognitive Performance and Synaptogenesis in the 5 × FAD Alzheimer Mouse Model. Molecular neurobiology. https://doi.org/10.1007/s12035-025-05037-7
Vancouver
Ma H, Chang Z, Sun H, Ma D, Li Z, Hao L, et al. A novel Dual GLP-1/CCK Receptor Agonist Improves Cognitive Performance and Synaptogenesis in the 5 × FAD Alzheimer Mouse Model. Molecular neurobiology. 2025. doi:10.1007/s12035-025-05037-7. PMID: 40338455.
BibTeX
@article{ma2025-40338455,
author = {Ma, H. and Chang, Z. and Sun, H. and Ma, D. and Li, Z. and Hao, L. and Zhang, Z. and Hölscher, C. and others},
title = {{A novel Dual GLP-1/CCK Receptor Agonist Improves Cognitive Performance and Synaptogenesis in the 5 × FAD Alzheimer Mouse Model}},
journal = {Molecular neurobiology},
year = {2025},
doi = {10.1007/s12035-025-05037-7},
pmid = {40338455},
url = {https://doi.org/10.1007/s12035-025-05037-7}
}
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Key findings
- In conclusion, the combination of GLP-1 and CCK receptor activation did not show overall improvements over single GLP-1 receptor activation.
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Study details
- Evidence strengthLow
How this study scored 41/100
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 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular neurobiology) |
| 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 “mouse”) — 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 40338455) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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Also tagged “fad”
2 studies in the library carry the topic tag “fad”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 2 tagged studies.