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Multi-omics framework prioritizes RNA Methylation Modification Genes in Alzheimer's Disease and Functional Validation of ZFP36 in Regulating Neuroinflammation
He D, Liu R, Tian Z, Xiong Z, Zhang K, Zheng X, Luo Z, Li X et al.. Research Square, 2026-10-21
Topic: Genetics and APOE
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, in which epitranscriptomic modifications, especially RNA methylation, may exert crucial regulatory effects. This study integrated bulk transcriptomics, single‑cell sequencing and machine learning to screen RNA methylation‑related genes in AD and explore the functional role of zinc finger protein 36 (ZFP36). We screened RNA methylation-related differentially expressed genes (DEGs) by overlapping AD-associated DEGs with RNA methylation-related genes using the GSE84422 dataset. Six hub genes (C3, ZFP36, S100A9, GADD45A, PHGDH, FBXW7) were screened via PPI centrality analysis, LASSO regression and random forest algorithms and validated in GSE122063. ssGSEA immune infiltration analysis showed ZFP36 had the strongest positive correlation with effector memory CD8+ T cell enrichment score. Single‑cell RNA‑seq of human prefrontal cortex samples revealed high ZFP36 expression in microglia, T cells and astrocytes. Consistent with the bioinformatic findings, in vivo experiments in 9‑month‑old 5xFAD mice verified that ZFP36 overexpression in the hippocampus improved spatial learning and memory. Cell experiments showed that ZFP36 overexpression alleviated LPS-induced inflammatory responses in microglia. Subsequent virtual screening identified the compound MCULE‑4171537037 with moderate binding affinity for ZFP36. These findings associate ZFP36 with AD-related neuroinflammatory features and support further evaluation of its potential as a candidate biomarker and therapeutic target.
Key findings
- Single‑cell RNA‑seq of human prefrontal cortex samples revealed high ZFP36 expression in microglia, T cells and astrocytes.
- Cell experiments showed that ZFP36 overexpression alleviated LPS-induced inflammatory responses in microglia.
- These findings associate ZFP36 with AD-related neuroinflammatory features and support further evaluation of its potential as a candidate biomarker and therapeutic target.
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Preprint — not yet peer-reviewed.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, 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 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 | 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 | 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 →
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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
He, D., Liu, R., Tian, Z., Xiong, Z., Zhang, K., Zheng, X., et al. (2026). Multi-omics framework prioritizes RNA Methylation Modification Genes in Alzheimer's Disease and Functional Validation of ZFP36 in Regulating Neuroinflammation. Research Square. https://doi.org/10.21203/rs.3.rs-10955695/v1
Vancouver
He D, Liu R, Tian Z, Xiong Z, Zhang K, Zheng X, et al. Multi-omics framework prioritizes RNA Methylation Modification Genes in Alzheimer's Disease and Functional Validation of ZFP36 in Regulating Neuroinflammation. Research Square. 2026. doi:10.21203/rs.3.rs-10955695/v1.
BibTeX
@article{he2026-24cbdbd1,
author = {He, D. and Liu, R. and Tian, Z. and Xiong, Z. and Zhang, K. and Zheng, X. and Luo, Z. and Li, X. and others},
title = {{Multi-omics framework prioritizes RNA Methylation Modification Genes in Alzheimer's Disease and Functional Validation of ZFP36 in Regulating Neuroinflammation}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10955695/v1},
url = {https://doi.org/10.21203/rs.3.rs-10955695/v1}
}
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