Document Type
Article
Publication Date
7-25-2025
Abstract
Due to their clinical heterogeneity, nonspecific symptoms, and the limitations of existing biomarkers and imaging modalities, metabolic brain diseases (MBDs), such as mitochondrial encephalopathies, lysosomal storage disorders, and glucose metabolism syndromes, pose significant diagnostic challenges. This review examines the growing potential of cell-free DNA (cfDNA) derived from cerebrospinal fluid (CSF) epigenetic profiling as a dynamic, cell-type-specific, minimally invasive biomarker approach for MBD diagnosis and monitoring. We review important technological platforms and their use in identifying CNS-specific DNA methylation patterns indicative of neuronal injury, neuroinflammation, and metabolic reprogramming, including cfMeDIP-seq, enzymatic methyl sequencing (EM-seq), and targeted bisulfite sequencing. By synthesizing current findings across disorders such as MELAS, Niemann-Pick disease, Gaucher disease, GLUT1 deficiency syndrome, and diabetes-associated cognitive decline, we highlight the superior diagnostic and prognostic resolution offered by CSF cfDNA methylation signatures relative to conventional CSF markers or neuroimaging. We also address technical limitations, interpretive challenges, and translational barriers to clinical implementation. Ultimately, this review explores CSF cfDNA epigenetic analysis as a liquid biopsy modality. The central objective is to assess whether epigenetic profiling of CSF-derived cfDNA can serve as a reliable and clinically actionable biomarker for improving the diagnosis and longitudinal monitoring of metabolic brain diseases.
Recommended Citation
Sporn, Kyle; Kumar, Rahul; Marla, Kiran; Ravi, Puja; Vaja, Swapna; Paladugu, Phani; Zaman, Nasif; and Tavakkoli, Alireza, "Epigenetic Profiling of Cell-Free DNA in Cerebrospinal Fluid: A Novel Biomarker Approach for Metabolic Brain Diseases" (2025). SKMC Student Presentations and Publications. Paper 69.
https://jdc.jefferson.edu/skmcstudentworks/69
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Language
English
Included in
Biological Factors Commons, Investigative Techniques Commons, Nervous System Diseases Commons, Nutritional and Metabolic Diseases Commons
Comments
This article is the author’s final published version in Life, Volume 15, Issue 8, 2025, Article number 1181.
The published version is available at https://doi.org/10.3390/life15081181. Copyright © 2025 by the authors.