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Electroacupuncture alleviate cognitive impairment via activation of TREM2-positive microglia in APP/PS1 mice
Tan Q, Xie A, Chen J, Wei S, Guo Y, Liu G, Wang L, Liu X et al.. Research Square, 2026-10-16
Topic: Inflammation, microglia and astrocytes
Background Microglial activation-mediated neuroinflammation and impaired Aβ phagocytosis are critical contributors to Alzheimer’s disease (AD) pathogenesis. Triggering receptor expressed on myeloid cells 2 (TREM2), a key microglial receptor, is closely implicated in AD by promoting Aβ clearance and limiting tau spreading. Electroacupuncture (EA) has been shown to alleviate microglial activation-induced neuroinflammation and restore impaired microglial phagocytosis in AD, yet whether it ameliorates cognitive deficits via TREM2 + microglial functional modulation remains elusive. Methods APP/PS1 mice received EA treatment, with or without intracerebroventricular injection of AAV-shTREM2 to knock down TREM2. Cognitive function was evaluated using the Morris Water Maze and Novel Object Recognition tests. Aβ deposition, neuronal injury, microglial phenotypic polarization, and TREM2 expression were detected via immunofluorescence, Western blotting (WB), and enzyme-linked immunosorbent assay (ELISA). Recruitment of TREM2 + microglial to Aβ plaques and their phagocytic activity (marked by CD68) were evaluated using triple immunofluorescence staining. Single-cell RNA sequencing (scRNA-seq) was conducted to characterize microglial heterogeneity and intercellular communication networks. Results EA ameliorated cognitive performance in APP/PS1 mice, attenuated neuronal damage and Aβ deposition, and upregulated the expression of TREM2 and DAP12. EA induced a shift of microglia from a pro‑inflammatory toward a repair‑associated phenotype, promoted recruitment of TREM2 + microglia to Aβ plaques, and enhanced their phagocytic activity. scRNA-seq analysis revealed that EA enriched a subpopulation of disease-associated microglia (DAM) and upregulated genes related to phagocytosis and lipid metabolism in this subpopulation. EA also inhibited pro-inflammatory intercellular signaling and potentiated protective intercellular communication. Conclusions EA ameliorated cognitive impairment in APP/PS1 mice by enhancing TREM2⁺ microglia-mediated Aβ clearance and suppressing neuroinflammation. scRNA-seq further revealed that EA reshaped microglial transcriptional states and intercellular communication networks in a TREM2-dependent manner. These
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APA 7th
Tan, Q., Xie, A., Chen, J., Wei, S., Guo, Y., Liu, G., et al. (2026). Electroacupuncture alleviate cognitive impairment via activation of TREM2-positive microglia in APP/PS1 mice. Research Square. https://doi.org/10.21203/rs.3.rs-11138446/v1
Vancouver
Tan Q, Xie A, Chen J, Wei S, Guo Y, Liu G, et al. Electroacupuncture alleviate cognitive impairment via activation of TREM2-positive microglia in APP/PS1 mice. Research Square. 2026. doi:10.21203/rs.3.rs-11138446/v1.
BibTeX
@article{tan2026-437238a8,
author = {Tan, Q. and Xie, A. and Chen, J. and Wei, S. and Guo, Y. and Liu, G. and Wang, L. and Liu, X. and others},
title = {{Electroacupuncture alleviate cognitive impairment via activation of TREM2-positive microglia in APP/PS1 mice}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-11138446/v1},
url = {https://doi.org/10.21203/rs.3.rs-11138446/v1}
}
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Key findings
- Results EA ameliorated cognitive performance in APP/PS1 mice, attenuated neuronal damage and Aβ deposition, and upregulated the expression of TREM2 and DAP12.
- EA induced a shift of microglia from a pro‑inflammatory toward a repair‑associated phenotype, promoted recruitment of TREM2 + microglia to Aβ plaques, and enhanced their phagocytic activity. scRNA-seq analysis revealed that EA enriched a subpopulation of disease-associated microglia (DAM) and upregulated genes related to phagocytosis and lipid metabolism in this subpopulation.
- Conclusions EA ameliorated cognitive impairment in APP/PS1 mice by enhancing TREM2⁺ microglia-mediated Aβ clearance and suppressing neuroinflammation. scRNA-seq further revealed that EA reshaped microglial transcriptional states and intercellular communication networks in a TREM2-dependent manner.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on 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 multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 |
| Randomised / blinded | 0 / 2 | No randomisation 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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