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miR155 triplicated in Down syndrome regulates hippocampal GABAergic neurogenesis in Alzheimer’s disease
Zhu X, Haure-Mirande J, Bicak M, Dong P, Kruglikov I, Al-subaie A, Fossati V, Noggle S et al.. bioRxiv, 2025-09-30
Topic: Genetics and APOE
MicroRNA dysregulation is implicated in neurodegenerative disorders, including Alzheimer’s disease (AD). The role of neuronal microRNA155 (miR155), elevated in both AD and Down syndrome (DS), remains unknown. We found that MIR155HG (miR155 host gene) colocalizes with APP (amyloid-beta precursor protein) in a neuron-specific, topologically-associated domain (TAD) within a regulatory network, in the obligate portion of chromosome 21 triplicated in DS which causes AD neuropathology and in most cases, dementia. We investigated miR155 role during neuron development and then validated these findings in an amyloidopathy model. In human induced pluripotent stem cell (hiPSC)-derived neural stem cells (NSCs), cortical neurons and cortical organoids, MIR155 deletion enhanced NSC proliferation, ventral patterning and GABAergic interneuron generation. However, MIR155 overexpression inhibited NSC marker expression and GABAergic interneuron generation. MIR155 upregulates its mRNA targets, NR2F1 / 2 , key modulators of hippocampal GABAergic interneuron development. In an amyloidopathy mouse model, miR155 deletion induced the expansion of hippocampal NSCs and increased hippocampal GABAergic interneurons. These findings reveal previously unrecognized miR155 roles in NSC dynamics and GABAergic interneuron development which directionally diverge from extensively studied microglial miR155 in their beneficial vs negative impact on AD mouse models, suggesting that approaching miR155 therapeutically may require balancing the effects in neurons and microglia.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zhu, X., Haure-Mirande, J., Bicak, M., Dong, P., Kruglikov, I., Al-subaie, A., et al. (2025). miR155 triplicated in Down syndrome regulates hippocampal GABAergic neurogenesis in Alzheimer’s disease. bioRxiv. https://doi.org/10.1101/2025.09.28.679053
Vancouver
Zhu X, Haure-Mirande J, Bicak M, Dong P, Kruglikov I, Al-subaie A, et al. miR155 triplicated in Down syndrome regulates hippocampal GABAergic neurogenesis in Alzheimer’s disease. bioRxiv. 2025. doi:10.1101/2025.09.28.679053.
BibTeX
@article{zhu2025-0e640888,
author = {Zhu, X. and Haure-Mirande, J. and Bicak, M. and Dong, P. and Kruglikov, I. and Al-subaie, A. and Fossati, V. and Noggle, S. and others},
title = {{miR155 triplicated in Down syndrome regulates hippocampal GABAergic neurogenesis in Alzheimer’s disease}},
journal = {bioRxiv},
year = {2025},
doi = {10.1101/2025.09.28.679053},
url = {https://doi.org/10.1101/2025.09.28.679053}
}
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.
Key findings
- We found that MIR155HG (miR155 host gene) colocalizes with APP (amyloid-beta precursor protein) in a neuron-specific, topologically-associated domain (TAD) within a regulatory network, in the obligate portion of chromosome 21 triplicated in DS which causes AD neuropathology and in most cases, dementia.
- We investigated miR155 role during neuron development and then validated these findings in an amyloidopathy model.
- These findings reveal previously unrecognized miR155 roles in NSC dynamics and GABAergic interneuron development which directionally diverge from extensively studied microglial miR155 in their beneficial vs negative impact on AD mouse models, suggesting that approaching miR155 therapeutically may require balancing the effects in neurons and microglia.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 19 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, studied in people 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 12 of the 62 points we could judge it on, which is 19 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| 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 | 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 | — / 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 | 12 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 12 of the 62 points we could judge it on is 19 out of 100. |
| Total | 19 / 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 →
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