<i>PDK4</i> as a metabolic biomarker of chronic hydrocephalus.
Overview
- Department of Biomedical and Electrical Engineering, Marshall University, Huntington, WV, United States
- Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States
- Department of Cardiothoracic Surgery, Southcoast Health, Fall River, MA, United States
- Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, United States
- Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States
Abstract
Background: Chronic hydrocephalus (CH) is a heterogeneous neurological disorder characterized by persistent ventricular enlargement and neurovascular dysfunction in the aging brain. Despite its clinical relevance, genetically anchored RNA biomarkers reflecting CH-associated metabolic and stress-related pathology remain poorly defined.
Methods: We performed bulk RNA sequencing of postmortem caudate nucleus tissue from individuals with CH and age-matched neurologically normal controls. Disease-associated transcriptional programs were identified using principal component analysis (PCA), unsupervised hierarchical clustering, and gene set enrichment analysis (GSEA). Key candidate transcripts were validated by RT-PCR. Comparative genomic analyses across mouse, rat, pig, and human genomes examined transcript length, chromosomal positioning, and nucleotide composition.
Results: PCA of the top 1,000 most variable transcripts demonstrated robust separation between CH and controls. Analysis of transcripts ranked 1,001–2,000 independently reproduced disease segregation, indicating distinct transcriptional programs. GSEA revealed significant enrichment of xenobiotic metabolism and oxidative stress pathways, with pyruvate dehydrogenase kinase 4 (PDK4) emerging as the top-ranked gene among ∼40,000 transcripts. RT-PCR confirmed robust PDK4 upregulation. Comparative genomics showed conserved transcript length but increased telomeric proximity and A+T content in humans.
Conclusion: PDK4: is identified as a prominent RNA marker of chronic hydrocephalus in the elderly, providing a neurogenomic foundation for future fluid-based RNA biomarker development.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 10 authors, 5 keywords, 3 funders, 95 references.
Cite
This paper
Clarke, R., Villers, P., Bills, C., Rice, M., Higgins, M., Lee, C., Patra, P., Lee, P. H., Moghekar, A., & Shim, J. W. (2026). &
BibTeX
@article{clarke2026lt,
author = {Clarke, Robbie and Villers, Payton and Bills, Chloe and Rice, Michaela and Higgins, Madison and Lee, Chan and Patra, Prabir and Lee, Peter HU and Moghekar, Abhay and Shim, Joon W},
title = {{\&
journal = {Frontiers in genetics},
year = {2026},
month = mar,
volume = {17},
pages = {1780231},
publisher = {Frontiers Media SA},
issn = {1664-8021},
doi = {10.3389/
url = {https://
pmid = {41938620},
pmcid = {PMC13043410}
}
RIS
TY - JOUR
AU - Clarke, Robbie
AU - Villers, Payton
AU - Bills, Chloe
AU - Rice, Michaela
AU - Higgins, Madison
AU - Lee, Chan
AU - Patra, Prabir
AU - Lee, Peter HU
AU - Moghekar, Abhay
AU - Shim, Joon W
TI - &
T2 - Frontiers in genetics
J2 - Front Genet
PY - 2026
DA - 2026/
VL - 17
SP - 1780231
SN - 1664-8021
PB - Frontiers Media SA
DO - 10.3389/
UR - https://
LA - en
ER -
CSL-JSON
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