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45/100

✓ Peer-reviewed alzhub usefulness score 45 out of 100. Inflammation and the immune system

Topic: Brain proteins, microglia and lab models

Plain-language summary

Cerebral small vessel disease (SVD) is frequently comorbid with Alzheimer's disease (AD), and brain endothelial cells (BECs) express genes associated with AD genetic risk. However, the epigenome of neurovascular cells and its intersection with genetic risk remain unexplored. Here, we generated gene regulomes for human BECs, mural cells, and other brain cell types and showed that AD heritability is primarily immune related, with a modest BEC enrichment. On the other hand, SVD heritability is enriched across the neurovascular unit, including astrocytes. Enhancer-to-gene interactomes implicated disease-distinct putative risk genes associated with amyloid and phospholipid processes in AD and senescence-associated pathways in SVD. Motifs for putative partners of lineage-determining transcription factors (TFs) in microglia and BECs were enriched for AD and SVD variants linked to disease-associated genes. In silico screening of compounds implicated vitamin D receptor agonists, mammalian target of rapamycin (mTOR), histone deacetylase (HDAC), and vascular endothelial growth factor receptor (VEGFR) inhibitors for AD. Our findings highlight regulatory mechanisms and therapeutic targets within the neurovascular system.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Ziegler, K. C., Askarova, A., Gergian, C., Yaa, R. M., van Dalen, J. D., Transfeld, J. L., et al. (2025). The brain neurovascular epigenome and its association with dementia. Neuron. https://doi.org/10.1016/j.neuron.2025.10.001

Vancouver

Ziegler KC, Askarova A, Gergian C, Yaa RM, van Dalen JD, Transfeld JL, et al. The brain neurovascular epigenome and its association with dementia. Neuron. 2025. doi:10.1016/j.neuron.2025.10.001. PMID: 41173000.

BibTeX

@article{ziegler2025-41173000,
  author  = {Ziegler, Kevin Chris and Askarova, Aydan and Gergian, Charbel and Yaa, Reuben M and van Dalen, Janna D. and Transfeld, Janis Lisa and Zoppi, Filippo and Du, Jia and others},
  title   = {{The brain neurovascular epigenome and its association with dementia}},
  journal = {Neuron},
  year    = {2025},
  doi     = {10.1016/j.neuron.2025.10.001},
  pmid    = {41173000},
  url     = {https://doi.org/10.1016/j.neuron.2025.10.001}
}

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How to read this study

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Effect: the record gives no effect size, so the summary above cannot say how large any difference was.

What the evidence grade means here

This page is graded low. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Low means the abstract matched neither pattern. It is the default label, and it does not mean the work is poor; many sound lab and imaging papers land here. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

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Key findings

Cerebral small vessel disease (SVD) is frequently comorbid with Alzheimer's disease (AD), and brain endothelial cells (BECs) express genes associated with AD genetic risk.
Here, we generated gene regulomes for human BECs, mural cells, and other brain cell types and showed that AD heritability is primarily immune related, with a modest BEC enrichment.
Enhancer-to-gene interactomes implicated disease-distinct putative risk genes associated with amyloid and phospholipid processes in AD and senescence-associated pathways in SVD.
Our findings highlight regulatory mechanisms and therapeutic targets within the neurovascular system.

Why it matters

This study mapped gene regulation in human brain vascular cells and found that Alzheimer's heritability is primarily immune related, while small vessel disease heritability involves the neurovascular unit. Computer screening suggested possible drug classes for Alzheimer's, but these are not proven treatments.

Study details

Evidence strengthLow

How this study scored 45/100

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.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Neuron)
Journal's citation record	4 / 4	Neuron: journal h-index 689 (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)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	2 / 7	Cited 10 times (OpenAlex, 2026-10-10)
Citations per year	2 / 5	3.3 citations a year over 3 year(s) since 2025
Impact for its field and year	3 / 6	Cited 5.5× 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 10 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	2 / 4	Last-listed author Alexi Nott: h-index 21 (OpenAlex, whole career)
Institution's track record	2 / 3	Inserm: institution h-index 1,988 (OpenAlex)
Multicenter collaboration	3 / 3	OpenAlex lists 13 institution(s) in 5 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 41173000)
Free to read	2 / 2	Free to read
Total	45 / 100	—

What each of these 20 components measures, and what this score is not →

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