Altered sphingolipid function in Alzheimer’s disease; a gene regulatory network approach.

Mar 29, 2021

Contributor: Caterina Giovagnoni,Muhammad Ali,Lars M T Eijssen,Richard Maes,Kyonghwan Choe,Monique Mulder,Jos Kleinjans,Antonio Del Sol,Enrico Glaab,Diego Mastroeni,Elaine Delvaux,Paul Coleman,Mario Losen,Ehsan Pishva,Pilar Martinez-Martinez,Daniel L A van den Hove

Altered sphingolipid function in Alzheimer’s disease; a gene regulatory network approach.

Sphingolipids (SLs) are bioactive lipids involved in various important physiological functions. The SL pathway has been shown to be affected in several brain-related disorders, including Alzheimer’s disease (AD). Recent evidence suggests that epigenetic dysregulation plays an important role in the pathogenesis of AD as well. Here, we use an integrative approach to better understand the relationship between epigenetic and transcriptomic processes in regulating SL function in the middle temporal gyrus of AD patients. Transcriptomic analysis of 252 SL-related genes, selected based on GO term annotations, from 46 AD patients and 32 healthy age-matched controls, revealed 103 differentially expressed SL-related genes in AD patients. Additionally, methylomic analysis of the same subjects revealed parallel hydroxymethylation changes in PTGIS, GBA, and ITGB2 in AD. Subsequent gene regulatory network-based analysis identified 3 candidate genes, that is, SELPLG, SPHK1 and CAV1 whose alteration holds the potential to revert the gene expression program from a diseased towards a healthy state. Together, this epigenomic and transcriptomic approach highlights the importance of SL-related genes in AD, and may provide novel biomarkers and therapeutic alternatives to traditionally investigated biological pathways in AD.

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About The Expert

Caterina Giovagnoni

School for Mental Health and Neuroscience (MHeNs), Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands. Electronic address: c.giovagnoni@maastrichtuniversity.nl.

Muhammad Ali

School for Mental Health and Neuroscience (MHeNs), Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands; Computational Biology Group, Luxembourg Centre for System Biomedicine (LCSB), University of Luxembourg, Belvaux, Luxembourg; Biomedical Data Science Group, Luxembourg Centre for System Biomedicine (LCSB), University of Luxembourg, Belvaux, Luxembourg.

Lars M T Eijssen

School for Mental Health and Neuroscience (MHeNs), Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands; Department of Bioinformatics – BiGCaT, NUTRIM, Maastricht University, Maastricht, the Netherlands.

Richard Maes

School for Mental Health and Neuroscience (MHeNs), Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands; Department of Bioinformatics – BiGCaT, NUTRIM, Maastricht University, Maastricht, the Netherlands.

Kyonghwan Choe

School for Mental Health and Neuroscience (MHeNs), Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands.

Monique Mulder

Department of Internal Medicine, Division of Pharmacology, Vascular and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

Jos Kleinjans

Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.

Antonio Del Sol

Computational Biology Group, Luxembourg Centre for System Biomedicine (LCSB), University of Luxembourg, Belvaux, Luxembourg; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; CIC bioGUNE, Bizkaia Technology Park, Derio, Spain.

Enrico Glaab

Biomedical Data Science Group, Luxembourg Centre for System Biomedicine (LCSB), University of Luxembourg, Belvaux, Luxembourg.

Diego Mastroeni

Biodesign Institute, Neurodegenerative Disease Research Center, Arizona State University, Tempe, AZ, USA.

Elaine Delvaux

Biodesign Institute, Neurodegenerative Disease Research Center, Arizona State University, Tempe, AZ, USA.

Paul Coleman

Biodesign Institute, Neurodegenerative Disease Research Center, Arizona State University, Tempe, AZ, USA.

Mario Losen

School for Mental Health and Neuroscience (MHeNs), Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands.

Ehsan Pishva

School for Mental Health and Neuroscience (MHeNs), Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands; University of Exeter Medical School, University of Exeter, Exeter, UK.

Pilar Martinez-Martinez

School for Mental Health and Neuroscience (MHeNs), Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands.

Daniel L A van den Hove

School for Mental Health and Neuroscience (MHeNs), Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands; Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.

References

PubMed