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. 2015 Feb;36(2):583-91.
doi: 10.1016/j.neurobiolaging.2014.09.027. Epub 2014 Oct 2.

Alzheimer's disease is associated with altered expression of genes involved in immune response and mitochondrial processes in astrocytes

Shobana Sekar  1 , Jacquelyn McDonald  1 , Lori Cuyugan  1 , Jessica Aldrich  2 , Ahmet Kurdoglu  2 , Jonathan Adkins  1 , Geidy Serrano  3 , Thomas G Beach  3 , David W Craig  2 , Jonathan Valla  4 , Eric M Reiman  5 , Winnie S Liang  6
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Alzheimer's disease is associated with altered expression of genes involved in immune response and mitochondrial processes in astrocytes

Shobana Sekar et al. Neurobiol Aging. 2015 Feb.

Abstract

Alzheimer's disease (AD) is characterized by deficits in cerebral metabolic rates of glucose in the posterior cingulate (PC) and precuneus in AD subjects, and in APOEε4 carriers, decades before the onset of measureable cognitive deficits. However, the cellular and molecular basis of this phenotype remains to be clarified. Given the roles of astrocytes in energy storage and brain immunity, we sought to characterize the transcriptome of AD PC astrocytes. Cells were laser capture microdissected from AD (n = 10) and healthy elderly control (n = 10) subjects for RNA sequencing. We generated >5.22 billion reads and compared sequencing data between controls and AD patients. We identified differentially expressed mitochondria-related genes including TRMT61B, FASTKD2, and NDUFA4L2, and using pathway and weighted gene coexpression analyses, we identified differentially expressed immune response genes. A number of these genes, including CLU, C3, and CD74, have been implicated in beta amyloid generation or clearance. These data provide key insights into astrocyte-specific contributions to AD, and we present this data set as a publicly available resource.

Keywords: Alzheimer's disease; Astrocytes; Immune response; Mitochondria; Posterior cingulate; RNA sequencing.

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Figures

Figure 1
Figure 1. Differentially expressed genes in AD PC astrocytes
Differentially expressed genes (corrected P<0.05) with the highest log2 fold changes are shown. *mitochondrial gene; **immune response gene
Figure 2
Figure 2. WGCNA dendrogram of differentially expressed genes in AD PC astrocytes
226 differentially expressed genes (corrected P<0.05) were used for WGCNA. (A) Seven coexpression modules were generated and the total genes for each module are as follows: blue=26, brown=22, green=14, gray=53, red=12, turquoise=83, yellow=16. Each open ended arm in the dendrogram represents a separate gene. (B) Genes falling within each module are listed.
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