Background: Epigenetic mechanisms as a potential underlying pathogenic mechanism of neurodegenerative diseases have been the scope of several studies performed so far. However, there is a gap in analyzing different forms of early-onset dementia to minimize the effect of aging and the use of Lymphoblastoid cell lines (LCLs) as a possible disease model for earlier clinical phases.
Method: We performed a genome-wide DNA methylation analysis in 64 samples (from prefrontal cortex and lymphoblastoid cell lines) from Alzheimer's Disease (AD) and Frontotemporal dementia (FTD) using the Illumina Infinium MethylationEPIC V2.0 array. The studied cohort included sporadic early-onset (sEOAD, sFTD-TP43, sFTD-Tau) and genetic subgroups of AD (PSEN1) and FTD (MAPT, GRN, C9orf72), with n = 5 subjects/group. We analyzed the differentially methylated positions (DMPs) using the Beta regression model, with age and sex as covariates, and all p-values adjusted by False Discovery Rate (FDR). Venn diagrams to visualize common genes between pairwise comparisons and heatmaps were performed to further explore the most important DMPs. Elastic Net logistic regression was used to obtain epigenetic diagnostic signatures. We also performed a correlation analysis of DNA methylation levels with Clariom D array gene expression data for the same cohort.
Result: Results showed hypermethylation in patients' groups as the most frequent finding in both tissues studied (Fig. 1). We identified common DMPs when comparing patients with healthy controls (CTRL) for each respective disease (Fig. 2, 3). Biological significance analysis revealed common pathways altered in AD and FTD affecting neuron development, metabolism, signal transduction and immune system pathways. These alterations were also found in LCLs, even some related to neuron development. We obtained diagnostic signatures to differentiate patients from CTRL. In the brain, CpG methylation presented an inverse correlation with gene expression, while in LCLs we observed mainly a positive correlation.
Conclusion: This study enhances our understanding about the biological pathways that are associated with neurodegeneration, describes differential methylation patterns, and suggests LCLs are a potential cell model for studying neurodegenerative diseases in early clinical phases.
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http://dx.doi.org/10.1002/alz.088732 | DOI Listing |
Methods
January 2025
Noselab GmbH, Widenmayerstr. 27, 80538 Munich, Germany.
Background: Diagnostics for neurodegenerative diseases lack non-invasive approaches suitable for early-stage biochemical screening and routine examination of neuropathology. Biomarkers of neurodegenerative diseases pass through the brain-nose interface (BNI) and accumulate in nasal secretion. Sample collection from the brain-nose interface presents a compelling prospect as basis for a non-invasive molecular diagnosis of neuropathologies.
View Article and Find Full Text PDFJ Neurosci Methods
January 2025
Neuroimage Analytics Laboratory and Biggs Institute Neuroimaging Core, Glenn Biggs Institute for Neurodegenerative Disorders, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Electronic address:
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View Article and Find Full Text PDFAgeing Res Rev
January 2025
Center for Global Health Research, Saveetha Medical College & Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:
Parkinson's disease (PD) is one of the most incapacitating neurodegenerative diseases (NDDs). PD is the second most common NDD worldwide which affects approximately 1 to 2 percent of people over 65 years. It is an attractive pursuit for artificial intelligence (AI) to contribute to and evolve PD treatments through drug repositioning by repurposing existing drugs, shelved drugs, or even candidates that do not meet the criteria for clinical trials.
View Article and Find Full Text PDFAgeing Res Rev
January 2025
Department of Cardiovascular Center, TheFirst Hospital of Jilin University, Changchun,Jilin, China.
Sirtuin-3 (SIRT3) in mitochondria has nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase activity. As such, SIRT3 is crucial in cardiovascular and neurodegenerative diseases. Advanced proteomics and transcriptomics studies have revealed that SIRT3 expression becomes altered when the heart or brain is affected by external stimuli or disease, such as diabetic cardiomyopathy, atherosclerosis, myocardial infarction, Alzheimer's disease, Huntington's disease, and Parkinson's disease.
View Article and Find Full Text PDFTalanta
January 2025
Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Materials Science, Hebei University, Baoding 071002, Hebei Province, PR China. Electronic address:
MicroRNAs (miRNAs) serve as potential biomarkers for many diseases such as cancer, neurodegenerative diseases and cardiovascular conditions. The portable and accurate detection of miRNA is of great significance for the early diagnosis, treatment optimization and prognostic evaluation of diseases. Herein, a photothermal/visual dual-mode assay for let-7a is developed utilizing oxidized 3, 3', 5, 5' - tetramethylbenzidine (oxTMB) as signal reporter.
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