2′-Fucosyllactose mitigates cognitive deficits in Alzheimer models: targeting amyloid pathology, oxidative stress, and synaptic plasticity
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".