Home › Research › Inflammation and the immune system
GPR6 Protects Medial Entorhinal Cortex in 5×FAD Mice from Early Pathology in Alzheimer’s Disease
Miao C, Wang Z, Zhang X, Li Y, Fu X, Zhou Y, Tian J, Cheng S et al.. Research Square, 2026-10-22
Topic: Inflammation, microglia and astrocytes
Alzheimer’s disease (AD) is characterized by progressive memory decline, with the medial entorhinal cortex (MEC) representing an early vulnerable hub for spatial cognition. Here, using 10× Visium spatial transcriptomics, we identified Gpr6 as a MEC-enriched and layer III-biased gene whose expression was reduced in 5×FAD mice and in the entorhinal cortex of human AD patients. Bilateral MEC-targeted Gpr6 overexpression in young 5×FAD mice ameliorated early spatial memory deficits. In vivo two-photon calcium imaging further revealed MEC layer II/III network hyperactivity in 5×FAD mice, together with disrupted spatial and directional coding. Gpr6 overexpression attenuated MEC neuronal hyperactivity, improved spatial coding, and enhanced the stability of spatial representations across contexts. These effects were observed in both Gpr6-overexpressing and neighboring non-overexpressing neurons, consistent with both cell-associated and local circuit-level effects. In parallel, MEC-targeted Gpr6 overexpression reduced local Aβ plaque burden, altered microglial morphology, and increased dendritic spine density. Together, these findings identify GPR6 as an AD-vulnerable molecular regulator in the MEC and suggest a potential entry point for understanding and modulating early entorhinal circuit dysfunction in AD.
Key findings
- In vivo two-photon calcium imaging further revealed MEC layer II/III network hyperactivity in 5×FAD mice, together with disrupted spatial and directional coding.
- Together, these findings identify GPR6 as an AD-vulnerable molecular regulator in the MEC and suggest a potential entry point for understanding and modulating early entorhinal circuit dysfunction in AD.
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Preprint — not yet peer-reviewed.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 “mice”) — 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. |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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
Miao, C., Wang, Z., Zhang, X., Li, Y., Fu, X., Zhou, Y., et al. (2026). GPR6 Protects Medial Entorhinal Cortex in 5×FAD Mice from Early Pathology in Alzheimer’s Disease. Research Square. https://doi.org/10.21203/rs.3.rs-10817939/v1
Vancouver
Miao C, Wang Z, Zhang X, Li Y, Fu X, Zhou Y, et al. GPR6 Protects Medial Entorhinal Cortex in 5×FAD Mice from Early Pathology in Alzheimer’s Disease. Research Square. 2026. doi:10.21203/rs.3.rs-10817939/v1.
BibTeX
@article{miao2026-b8fc93ce,
author = {Miao, C. and Wang, Z. and Zhang, X. and Li, Y. and Fu, X. and Zhou, Y. and Tian, J. and Cheng, S. and others},
title = {{GPR6 Protects Medial Entorhinal Cortex in 5×FAD Mice from Early Pathology in Alzheimer’s Disease}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10817939/v1},
url = {https://doi.org/10.21203/rs.3.rs-10817939/v1}
}
Related studies in Inflammation and the immune system
Also tagged “dendritic”
287 studies in the library carry the topic tag “dendritic”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 287 tagged studies.