DNA methylation patterns contribute to changes of cellular differentiation pathways in leukocytes with LOY from patients with Alzheimer´s disease
Marcin Jąkalski, Bożena Bruhn‐Olszewska, Edyta Rychlicka-Buniowska, Hanna Davies, Daniil Sarkisyan, Maciej Siedlar, Jarosław Baran, Kazimierz Węglarczyk et al.. Cellular and Molecular Life Sciences, 2025-02-25
Topic: Brain proteins, microglia and lab models
Alzheimer's disease (AD) is a common and increasing societal problem due to the extending human lifespan. In males, loss of chromosome Y (LOY) in leukocytes is strongly associated with AD. We studied here DNA methylation and RNA expression in sorted monocytes and granulocytes with and without LOY from male AD patients. Through multi-omic analysis, we identified new candidate genes along with those previously associated with AD. Global analyses of DNA methylation in samples with LOY vs. normal state showed that hypomethylation dominated both in granulocytes and monocytes. Our findings highlight LOY-related differences in DNA methylation that occur in gene regulatory regions. Specifically, we observed alterations in key genes involved in leukocyte differentiation: FLI1, involved in early hematopoiesis; RUNX1, essential for blood cell development; RARA, regulating gene expression in response to retinoic acid; CANX, crucial for protein folding; CEBPB, a transcription factor important for immune responses; and MYADM, implicated in cell adhesion and migration. Moreover, protein-protein interaction analysis in granulocytes identified that products of two of these genes, CANX and CEBPB, are key hub proteins. This research underscores the potential of multi-omic approach in pure hematopoietic cell populations to uncover the molecular underpinnings of AD. Finally, our results link previous analysis showing impact of LOY on leukocyte differentiation, LOY-associated transcriptional dysregulation and GWAS studies of LOY.
Key findings
- In males, loss of chromosome Y (LOY) in leukocytes is strongly associated with AD.
- Through multi-omic analysis, we identified new candidate genes along with those previously associated with AD.
- Global analyses of DNA methylation in samples with LOY vs. normal state showed that hypomethylation dominated both in granulocytes and monocytes.
- Our findings highlight LOY-related differences in DNA methylation that occur in gene regulatory regions.
- Specifically, we observed alterations in key genes involved in leukocyte differentiation: FLI1, involved in early hematopoiesis; RUNX1, essential for blood cell development; RARA, regulating gene expression in response to retinoic acid; CANX, crucial for protein folding; CEBPB, a transcription factor important for immune responses; and MYADM, implicated in cell adhesion and migration.
Why it matters
This laboratory study examined DNA methylation and RNA expression in blood cells with and without loss of chromosome Y from male Alzheimer patients, finding changes in genes involved in leukocyte differentiation. It reports no treatment, cure, or prevention findings.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cellular and Molecular Life Sciences) |
| Journal's citation record | 3 / 4 | Cellular and Molecular Life Sciences: journal h-index 329 (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 | 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 | 1 / 7 | Cited 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.0× 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 | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Jan Piotr Dumanski: h-index 53 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Toronto: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39998604) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1007/s00018-025-05618-8
- PubMed: 39998604
- Original source →
- Free full text: Cellular and Molecular Life Sciences →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Jąkalski, M., Bruhn‐Olszewska, B., Rychlicka-Buniowska, E., Davies, H., Sarkisyan, D., Siedlar, M., et al. (2025). DNA methylation patterns contribute to changes of cellular differentiation pathways in leukocytes with LOY from patients with Alzheimer´s disease. Cellular and Molecular Life Sciences. https://doi.org/10.1007/s00018-025-05618-8
Vancouver
Jąkalski M, Bruhn‐Olszewska B, Rychlicka-Buniowska E, Davies H, Sarkisyan D, Siedlar M, et al. DNA methylation patterns contribute to changes of cellular differentiation pathways in leukocytes with LOY from patients with Alzheimer´s disease. Cellular and Molecular Life Sciences. 2025. doi:10.1007/s00018-025-05618-8. PMID: 39998604.
BibTeX
@article{jakalski2025-39998604,
author = {Jąkalski, Marcin and Bruhn‐Olszewska, Bożena and Rychlicka-Buniowska, Edyta and Davies, Hanna and Sarkisyan, Daniil and Siedlar, Maciej and Baran, Jarosław and Węglarczyk, Kazimierz and others},
title = {{DNA methylation patterns contribute to changes of cellular differentiation pathways in leukocytes with LOY from patients with Alzheimer´s disease}},
journal = {Cellular and Molecular Life Sciences},
year = {2025},
doi = {10.1007/s00018-025-05618-8},
pmid = {39998604},
url = {https://doi.org/10.1007/s00018-025-05618-8}
}
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