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- W2470083676 abstract "Gene expression is a fundamental mechanism in susceptibility to and manifestation of complex disease. We performed transcriptome analysis and weighted gene co-expression network analysis in late onset Alzheimer's disease (LOAD) using microarray gene expression profiles from the Alzheimer's Disease Neuroimaging Initiative (ADNI). 715 ADNI participants with Affymetrix Human Genome U219 Array data from peripheral blood samples (PaxGene RNA tubes) were included. Raw expression values were pre-processed using the Robust Multi-chip Average normalization followed by standard quality control (QC) procedures on samples and probe sets. Statistical analysis of microarray data was performed using the regularized t-test to evaluate differences in gene expression between AD and cognitively normal controls (HC), weighted gene co-expression network analysis to identify clusters of highly correlated genes, and MetaCore to perform a gene-set enrichment analysis. Data were adjusted for age, gender, plate, four principal components from multidimensional scaling, and RIN score (RNA integrity number). Significant associations were determined using FDR adjustment for multiple testing. Of the 18,866 probe sets represented on the array after QC, 27 probe sets (23 genes) were significantly up-regulated and 15 probe sets (15 genes) were significantly down-regulated in LOAD after controlling for multiple testing (corrected p<0.05) (Fig. 1). The most significantly altered gene was MAPK14 (up-regulated; corrected p=0.0087; Fig. 2). Network analysis identified two modules associated with diagnosis. The modules consisted of altered genes involved in immune response and mitochondrial processes, respectively (Fig. 3). RNA from peripheral blood indicated a differential gene expression pattern between AD patients and controls. MAPK14 critically regulates the immunological response in astrocytes (Selvaraj et al. 2014). Peripheral blood cells have been shown to share significant gene expression similarities with multiple central nervous system tissues, sharing more than 80% of the transcriptome with brain tissues (Liew et al. 2006). Gene expression signature in peripheral blood is a promising and accessible marker that can reveal novel cellular and molecular mechanisms that may contribute to LOAD." @default.
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- W2470083676 date "2015-07-01" @default.
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- W2470083676 title "P4-197: Gene expression profiling identifies altered networks in late-onset Alzheimer's disease: Immune response and mitochondrial process" @default.
- W2470083676 doi "https://doi.org/10.1016/j.jalz.2015.08.025" @default.
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