Identification of common molecular biomarker signatures in blood and brain of Alzheimer’s disease

Abstract

Background: Alzheimers disease (AD) is a progressive neurodegenerative disease characterized by memory loss and confusion. Neuroimaging and cerebrospinal fluid-based early detection is limited in sensitivity and specificity as well as by cost. Therefore, detecting AD from blood cell analysis could improve early diagnosis and treatment of the disease. The present study aimed to identify blood cell transcripts that reflect brain expression levels of factors linked to AD progression. Methods: We analyzed blood cell and brain microarray gene expression datasets from NCBI-GEO for AD association and expression in blood and brain. We also used eQTL and epigenetics data to identify AD-related genes that were regulated similarly in blood and brain. Results: We identified 9 differentially expressed genes (DEG; AD versus controls) common to blood cells and brain (CNBD1, SUCLG2-AS1, CCDC65, PDE4D, MTMR1, C3, SLC6A15, LINC01806, and FRG1JP) and 18 genes (HSD17B1, GAS5, RPS5, VKORC1, GLE1, WDR1, RPL12, MORN1, RAD52, SDR39U1, NPHP4, MT1E, SORD, LINC00638, MCM3AP-AS1, GSDMD, RPS9, and GNL2) that were commonly dysregulated between AD blood and brain tissues using SNP and cis-eQTL data. This data revealed significant neurodegeneration-associated molecular pathways in the ribosomal and complement systems. Integration of these different analyses revealed dysregulation of hub transcription factors (SREBF2, NR1H2, NR1H3, PRDM1, XBP1) and microRNAs (miR-518e, miR-518a-3p, miR-518b, miR-518c, miR-518d-3p and miR-518f) in AD. Several significant histone modification sites in DEGs were also identified. Conclusion: We have identified new putative links between pathological processes in brain and transcripts in blood cells in AD subjects that may enable the use of blood to diagnose and monitor AD onset and progression.

Identification of biomarkers and pathways to identify novel therapeutic targets in Alzheimer’s disease: Insights from a systems biomedicine perspective

“…Microarrays and RNA-seq are extensively used in biomedical research as the main resources of biomarker candidates form complex diseases [4][5][6]40]. Microarray gene expression profiling is widely used to identify DEGs in various diseases including AD [4][5][6]40]. Analyzing the gene expression patterns in the blood of the AD patients revealed significant alterations in the expression profiles of 25 common DEGs in two transcriptomics datasets.…”

“…The major fraction of AD patients diagnosed are late onset (over 65 years age) while only a small fraction (1-5%) are diagnosed early, but early diagnosis of AD is essential for management strategies of patients. Therefore, research directing towards exploring biomarkers may have impact on the complex diseases including AD diagnosis and treatment [3][4][5][6].…”

“…The dysregulation of the miRNAs are implicated in AD [21][22][23]. Consequently, miRNAs are increasingly being studied in the exploration of biomarkers in the AD [4][5]. Therefore, systems biology analyses are used to elucidate the possible roles of biomolecules in different complex diseases [4][5].…”

“…Consequently, miRNAs are increasingly being studied in the exploration of biomarkers in the AD [4][5]. Therefore, systems biology analyses are used to elucidate the possible roles of biomolecules in different complex diseases [4][5]. Accordingly, to identify critical genes, we used two peripheral blood microarray gene expression datasets.…”

Protein Expression Patterns in ovarian cancer cells Associated with Monofunctional Platinums Treatment

“…However, to systematically address the problem of cisplatin resistance we need to understand the alterations in cellular pathways that underlie this phenomenon, and endow cells with a survival advantage in patients being treatment. Such pathways may enable the cell to ignore growth inhibitory signals, to inappropriately block pro-apoptotic signals or to survive toxic chemical effects of the drug until serum levels of the drug fall [21,25].…”