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Common pathogenic mechanisms in the hippocampus across neurodegenerative dementias: Alzheimer’s disease, Down syndrome, and Parkinson’s disease
René A. J. Crans, Marta Fructuoso, Karen Bascon Cardozo, Hatice Recaioglu, Jesus Sotelo-Fonseca, Yannick Vermeiren, André Strydom, Debby Van Dam et al.. npj Dementia, 2026-04-29
Topic: Brain proteins, microglia and lab models
Abstract Extensive evidence suggests overlapping pathological mechanisms in the brain of individuals with Parkinson´s disease dementia, Down syndrome dementia, and Alzheimer´s disease. For these neurodegenerative dementias, we observed that the chronological age did not align with their biological age, which was determined based on hippocampal transcript levels (i.e., transcriptional age). Subsequently, we performed a transcriptomic analysis that corrected for the transcriptional age in the hippocampus of affected individuals, highlighting common underlying pathogenic mechanisms. There were 45 common differentially expressed genes (DEGs), whereas enriched functional terms were related to lysine N-methyltransferase activity and intermediate filament. Co-expression network analysis displayed a module that was significantly downregulated in the non-demented control group only. This module identified EHMT2 and LMNB2 as hub genes, which were also common DEGs. Overall, these findings uncover shared functional insights in the hippocampus, while specifically highlighting EHMT2 and LMNB2 as potential universal biomarkers or disease-altered targets across neurodegenerative dementias.
Key findings
- For these neurodegenerative dementias, we observed that the chronological age did not align with their biological age, which was determined based on hippocampal transcript levels (i.e., transcriptional age).
- Co-expression network analysis displayed a module that was significantly downregulated in the non-demented control group only.
- Overall, these findings uncover shared functional insights in the hippocampus, while specifically highlighting EHMT2 and LMNB2 as potential universal biomarkers or disease-altered targets across neurodegenerative dementias.
Why it matters
Looking at gene activity in the hippocampus, a memory hub, of people with Alzheimer's disease, Down syndrome dementia and Parkinson's disease dementia, researchers found 45 genes changed in common across all three conditions. Two of these, EHMT2 and LMNB2, stood out as central 'hub' genes in a shared network. The authors suggest they could be universal biomarkers or targets across these dementias, but this is an early gene-expression finding rather than a test of any treatment.
Study details
- Evidence strengthLow
How this study scored 32/100
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. We have no data on senior author's track record, so that was left out: it earned 31 of the 96 points we could judge it on, which is 32 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (npj Dementia) |
| Journal's citation record | 0 / 4 | Npj Dementia: journal h-index 10 (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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 0 / 6 | Cited 0.0× 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 | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Mara Dierssen holds only 5 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 1 / 3 | University of Groningen: institution h-index 1,383 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 13 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42078116) |
| Free to read | 2 / 2 | Free to read |
| Points | 31 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 31 of the 96 points we could judge it on is 32 out of 100. |
| Total | 32 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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
Crans, R. A. J., Fructuoso, M., Cardozo, K. B., Recaioglu, H., Sotelo-Fonseca, J., Vermeiren, Y., et al. (2026). Common pathogenic mechanisms in the hippocampus across neurodegenerative dementias: Alzheimer’s disease, Down syndrome, and Parkinson’s disease. npj Dementia. https://doi.org/10.1038/s44400-026-00075-x
Vancouver
Crans RAJ, Fructuoso M, Cardozo KB, Recaioglu H, Sotelo-Fonseca J, Vermeiren Y, et al. Common pathogenic mechanisms in the hippocampus across neurodegenerative dementias: Alzheimer’s disease, Down syndrome, and Parkinson’s disease. npj Dementia. 2026. doi:10.1038/s44400-026-00075-x. PMID: 42078116.
BibTeX
@article{crans2026-42078116,
author = {Crans, René A. J. and Fructuoso, Marta and Cardozo, Karen Bascon and Recaioglu, Hatice and Sotelo-Fonseca, Jesus and Vermeiren, Yannick and Strydom, André and Van Dam, Debby and others},
title = {{Common pathogenic mechanisms in the hippocampus across neurodegenerative dementias: Alzheimer’s disease, Down syndrome, and Parkinson’s disease}},
journal = {npj Dementia},
year = {2026},
doi = {10.1038/s44400-026-00075-x},
pmid = {42078116},
url = {https://doi.org/10.1038/s44400-026-00075-x}
}
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