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Epigenomic aberrations of histone methylation in prefrontal cortex of humans with mild cognitive impairment and Alzheimer's disease
Prachetas Jai Patel, Zhen Yan. Journal of Alzheimer s Disease, 2026-01-21
Topic: Brain proteins, microglia and lab models
BackgroundEpigenetic mechanisms, particularly histone modifications at gene promoters, are crucial for controlling gene transcription.ObjectiveWe aim to find out epigenomic aberrations during the progression of neurodegenerative disorders.MethodsWe employed a multifaceted approach to investigate how the two key histone methylation marks, H3K4me3 (linked to gene activation) and H3K27me3 (linked to gene suppression), are altered in postmortem prefrontal cortex of humans with mild cognitive impairment (MCI) or Alzheimer's disease (AD).ResultsCompared to controls, MCI and AD exhibited pronounced losses of permissive H3K4me3 peaks at promoters of genes enriched in synaptic plasticity and neurotransmission, and significant gains of H3K4me3 peaks at promoters of genes enriched in transcriptional regulation. AD displayed more substantial H3K4me3 losses on synaptic genes than MCI. Conversely, significant gains of repressive H3K27me3 peaks were observed at synaptic gene promoters in both disease groups, with MCI exhibiting more pronounced H3K27me3 gains on synaptic genes than AD. Weighted Gene Correlation Network Analysis (WGCNA) revealed multiple modules characterizing distinct patterns of gains and losses of H3K4me3 and H3K27me3 during the transition from MCI to AD. Integrative analysis of epigenomic and transcriptomic data indicated that these histone mark alterations were well correlated with the downregulation of synaptic genes and upregulation of transcriptional regulators in AD.ConclusionsThis comprehensive profiling uncovers a stage-dependent reorganization of histone modifications at critical gene loci, implicating these events in the molecular cascade of AD pathogenesis. Targeting dysregulated chromatin states may offer novel therapeutic avenues for early intervention of AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Patel, P. J., & Yan, Z. (2026). Epigenomic aberrations of histone methylation in prefrontal cortex of humans with mild cognitive impairment and Alzheimer's disease. Journal of Alzheimer s Disease. https://doi.org/10.1177/13872877251414887
Vancouver
Patel PJ, Yan Z. Epigenomic aberrations of histone methylation in prefrontal cortex of humans with mild cognitive impairment and Alzheimer's disease. Journal of Alzheimer s Disease. 2026. doi:10.1177/13872877251414887. PMID: 41560705.
BibTeX
@article{patel2026-41560705,
author = {Patel, Prachetas Jai and Yan, Zhen},
title = {{Epigenomic aberrations of histone methylation in prefrontal cortex of humans with mild cognitive impairment and Alzheimer's disease}},
journal = {Journal of Alzheimer s Disease},
year = {2026},
doi = {10.1177/13872877251414887},
pmid = {41560705},
url = {https://doi.org/10.1177/13872877251414887}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- BackgroundEpigenetic mechanisms, particularly histone modifications at gene promoters, are crucial for controlling gene transcription.ObjectiveWe aim to find out epigenomic aberrations during the progression of neurodegenerative disorders.MethodsWe employed a multifaceted approach to investigate how the two key histone methylation marks, H3K4me3 (linked to gene activation) and H3K27me3 (linked to gene suppression), are altered in postmortem prefrontal cortex of humans with mild cognitive impairment (MCI) or Alzheimer's disease (AD).ResultsCompared to controls, MCI and AD exhibited pronounced losses of permissive H3K4me3 peaks at promoters of genes enriched in synaptic plasticity and neurotransmission, and significant gains of H3K4me3 peaks at promoters of genes enriched in transcriptional regulation.
- Conversely, significant gains of repressive H3K27me3 peaks were observed at synaptic gene promoters in both disease groups, with MCI exhibiting more pronounced H3K27me3 gains on synaptic genes than AD.
- Weighted Gene Correlation Network Analysis (WGCNA) revealed multiple modules characterizing distinct patterns of gains and losses of H3K4me3 and H3K27me3 during the transition from MCI to AD.
- Integrative analysis of epigenomic and transcriptomic data indicated that these histone mark alterations were well correlated with the downregulation of synaptic genes and upregulation of transcriptional regulators in AD.ConclusionsThis comprehensive profiling uncovers a stage-dependent reorganization of histone modifications at critical gene loci, implicating these events in the molecular cascade of AD pathogenesis.
Why it matters
In postmortem prefrontal cortex, people with mild cognitive impairment and Alzheimer's disease showed losses of activating histone marks at synaptic genes and gains of repressive marks at synaptic gene promoters. This describes epigenomic changes during disease progression, not a treatment or cure.
Study details
- Evidence strengthLow
How this study scored 33/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 32 of the 96 points we could judge it on, which is 33 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer s Disease) |
| Journal's citation record | 2 / 4 | Journal of Alzheimer s Disease: journal h-index 218 (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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 2 / 6 | Cited 1.9× 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 | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Zhen Yan holds only 4 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 1 / 3 | University at Buffalo, State University of New York: institution h-index 918 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41560705) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 32 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 32 of the 96 points we could judge it on is 33 out of 100. |
| Total | 33 / 100 | — |
What each of these 20 components measures, and what this score is not →
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