Home › Research › Disease mechanisms
2′-Fucosyllactose mitigates cognitive deficits in Alzheimer models: targeting amyloid pathology, oxidative stress, and synaptic plasticity
Yeasmin Akter Munni, Khoa Nguyen Tran, Seon-min Jeon, Meeyul Hwang, Jong-Won Yoon, Young‐Ha Song, Tae Woo Oh, Sang Il Gum et al.. Frontiers in Pharmacology, 2025-08-21
Topic: Brain proteins, microglia and lab models
Introduction The development of new drugs for Alzheimer’s disease (AD) remains a major challenge due to the disorder’s complex and multifactorial nature. 2′-Fucosyllactose (2′-FL), a human milk oligosaccharide, has demonstrated promising neuroprotective properties. However, its effects on AD-related cognitive decline are not yet fully understood. This study aimed to investigate the therapeutic potential of 2′-FL in an aging mouse model of AD and to explore the underlying mechanisms involved. Methods 5xFAD transgenic mice were treated with 2′-FL and assessed for cognitive function using the Morris water maze and Y-maze tests. Immunohistochemical staining was used to evaluate amyloid-beta (Aβ) and phosphorylated tau (p-tau) levels in brain tissue samples. Blood samples were analyzed to determine circulating cytokine levels. Additionally, BV2 microglial cells and primary hippocampal neurons (PHNs) were used in vitro to investigate the effects of 2′-FL on neuroinflammation, oxidative stress, and synaptic plasticity. Results 2′-FL (300–1,200 mg/kg, oral) improved cognitive performance in 5xFAD mice by shortening escape latency in the water maze and restoring alternation behavior in the Y-maze test. It significantly reduced Aβ plaque load in the hippocampus and cortex but did not significantly affect tau hyperphosphorylation. Furthermore, 2′-FL lowered plasma tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels. In BV2 cells, it suppressed d-galactose-induced neuroinflammation by downregulating TNF-α and IL-6, and nuclear factor-κB signaling. In PHNs, 2′-FL reduced oxidative stress, restored mitochondrial function, and limited DNA damage. Additionally, it counteracted d-galactose-induced synaptic deficits by promoting neurite outgrowth, enhancing synaptic vesicle recycling, and upregulating the synaptic markers brain-derived neurotrophic factor, postsynaptic density protein-95, and synaptic vesicle protein 2. Conclusion 2′-FL improved cognitive performance in 5xFAD mice, reduced Aβ plaque deposition and pro-inflammatory cytokine levels in vivo , and mitigated oxidative stress and synaptic dysfunction in cellular models. These findings indicate that 2′-FL modulates multiple pathological features relevant to AD in preclinical models.
Key findings
- Introduction The development of new drugs for Alzheimer’s disease (AD) remains a major challenge due to the disorder’s complex and multifactorial nature. 2′-Fucosyllactose (2′-FL), a human milk oligosaccharide, has demonstrated promising neuroprotective properties.
- Results 2′-FL (300–1,200 mg/kg, oral) improved cognitive performance in 5xFAD mice by shortening escape latency in the water maze and restoring alternation behavior in the Y-maze test.
- It significantly reduced Aβ plaque load in the hippocampus and cortex but did not significantly affect tau hyperphosphorylation.
- These findings indicate that 2′-FL modulates multiple pathological features relevant to AD in preclinical models.
Why it matters
In a mouse model of Alzheimer's disease, oral 2'-Fucosyllactose improved cognitive test performance and reduced amyloid plaque load in the hippocampus and cortex, but it did not significantly affect tau hyperphosphorylation. These findings are from animal and cell experiments, so it is not yet known whether this compound would help people.
Study details
- Evidence strengthLow
How this study scored 32/100
Published in a peer-reviewed 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 | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in Pharmacology) |
| Journal's citation record | 2 / 4 | Frontiers in Pharmacology: journal h-index 242 (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) |
| Randomised / blinded | 0 / 2 | No randomisation 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 0.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author In‐Jun Yang: h-index 19 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Korea University of Science and Technology: institution h-index 336 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40918527) |
| Free to read | 2 / 2 | Free to read |
| Total | 32 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fphar.2025.1598030
- PubMed: 40918527
- Original source →
- Free full text: Frontiers in Pharmacology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Munni, Y. A., Tran, K. N., Jeon, S.-m., Hwang, M., Yoon, J.-W., Song, Y., et al. (2025). 2′-Fucosyllactose mitigates cognitive deficits in Alzheimer models: targeting amyloid pathology, oxidative stress, and synaptic plasticity. Frontiers in Pharmacology. https://doi.org/10.3389/fphar.2025.1598030
Vancouver
Munni YA, Tran KN, Jeon S.-m, Hwang M, Yoon J.-W, Song Y, et al. 2′-Fucosyllactose mitigates cognitive deficits in Alzheimer models: targeting amyloid pathology, oxidative stress, and synaptic plasticity. Frontiers in Pharmacology. 2025. doi:10.3389/fphar.2025.1598030. PMID: 40918527.
BibTeX
@article{munni2025-40918527,
author = {Munni, Yeasmin Akter and Tran, Khoa Nguyen and Jeon, Seon-min and Hwang, Meeyul and Yoon, Jong-Won and Song, Young‐Ha and Oh, Tae Woo and Gum, Sang Il and others},
title = {{2′-Fucosyllactose mitigates cognitive deficits in Alzheimer models: targeting amyloid pathology, oxidative stress, and synaptic plasticity}},
journal = {Frontiers in Pharmacology},
year = {2025},
doi = {10.3389/fphar.2025.1598030},
pmid = {40918527},
url = {https://doi.org/10.3389/fphar.2025.1598030}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Related studies in Disease mechanisms
Also tagged “mice”
1,150 studies in the library carry the topic tag “mice”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,150 tagged studies.