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Electrical stimulation of the vagus nerve improves amyloid pathology in delirium superimposed on dementia
Chengcheng Song, Pau Yen Wu, William J. Huffman, Jennifer David‐Bercholz, Alicia Bedolla, Ravikanth Velagapudi, Ann Wangechi Njoroge, Ramona M. Rodriguiz et al.. Bioelectronic Medicine, 2026-01-16
Topic: Brain proteins, microglia and lab models
In AD-like mice surgery induced acute changes in amyloid-β; perioperative treatment with pVNS effectively reduced amyloid-β load, plaque sphericity, and neuronal loss. The rescue of these pathological hallmarks led to improved delirium-like behavior, as demonstrated by the 5-choice serial reaction time task on postoperative days 1 and 2. pVNS improved microglial morphology, particularly near amyloid-β plaques. Acute isolation of microglial cells from 5xFAD mice after surgery indicated that pVNS partially enhanced key Disease-Associated Microglia (DAM) markers. The contribution of pro-inflammatory cytokines to amyloid-β aggregation was validated using an in vitro transwell culture model following Cytomix exposure, which also caused endothelial barrier disruption. Finally, we isolated IL-6 as a well-established biomarker of postoperative delirium and described its role in DSD pathology following systemic administration. These findings establish a role for neuromodulation after pVNS in regulating perioperative immunity and advance a new paradigm for perioperative interventions in patients at risk for DSD.
Key findings
- In AD-like mice surgery induced acute changes in amyloid-β; perioperative treatment with pVNS effectively reduced amyloid-β load, plaque sphericity, and neuronal loss.
- The rescue of these pathological hallmarks led to improved delirium-like behavior, as demonstrated by the 5-choice serial reaction time task on postoperative days 1 and 2. pVNS improved microglial morphology, particularly near amyloid-β plaques.
- Acute isolation of microglial cells from 5xFAD mice after surgery indicated that pVNS partially enhanced key Disease-Associated Microglia (DAM) markers.
- The contribution of pro-inflammatory cytokines to amyloid-β aggregation was validated using an in vitro transwell culture model following Cytomix exposure, which also caused endothelial barrier disruption.
- Finally, we isolated IL-6 as a well-established biomarker of postoperative delirium and described its role in DSD pathology following systemic administration.
Why it matters
In Alzheimer's-like mice, vagus nerve stimulation around surgery reduced amyloid-beta load and neuronal loss and improved delirium-like behavior. This is early animal work, and it is not known whether the approach would help people.
Study details
- Evidence strengthLow
How this study scored 40/100
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 (Bioelectronic Medicine) |
| Journal's citation record | 0 / 4 | Bioelectronic Medicine: journal h-index 38 (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 | 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 | 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 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 10.1× 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 | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Niccolò Terrando: h-index 44 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Duke University: institution h-index 1,541 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41540503) |
| Free to read | 2 / 2 | Free to read |
| Total | 40 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s42234-025-00194-5
- PubMed: 41540503
- Original source →
- Free full text: Bioelectronic Medicine →
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
Song, C., Wu, P. Y., Huffman, W. J., David‐Bercholz, J., Bedolla, A., Velagapudi, R., et al. (2026). Electrical stimulation of the vagus nerve improves amyloid pathology in delirium superimposed on dementia. Bioelectronic Medicine. https://doi.org/10.1186/s42234-025-00194-5
Vancouver
Song C, Wu PY, Huffman WJ, David‐Bercholz J, Bedolla A, Velagapudi R, et al. Electrical stimulation of the vagus nerve improves amyloid pathology in delirium superimposed on dementia. Bioelectronic Medicine. 2026. doi:10.1186/s42234-025-00194-5. PMID: 41540503.
BibTeX
@article{song2026-41540503,
author = {Song, Chengcheng and Wu, Pau Yen and Huffman, William J. and David‐Bercholz, Jennifer and Bedolla, Alicia and Velagapudi, Ravikanth and Njoroge, Ann Wangechi and Rodriguiz, Ramona M. and others},
title = {{Electrical stimulation of the vagus nerve improves amyloid pathology in delirium superimposed on dementia}},
journal = {Bioelectronic Medicine},
year = {2026},
doi = {10.1186/s42234-025-00194-5},
pmid = {41540503},
url = {https://doi.org/10.1186/s42234-025-00194-5}
}
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