title: Alzheimer's disease is associated with altered expression of genes involved in immune response and mitochondrial processes in astrocytes.
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.
authors.affiliation: Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA; Arizona Alzheimer's Consortium, Phoenix, AZ, USA.
authors.forename: Shobana
authors.initials: S
authors.lastname: Sekar
authors.affiliation: Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA; Arizona Alzheimer's Consortium, Phoenix, AZ, USA.
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: McDonald
authors.affiliation: Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA; Arizona Alzheimer's Consortium, Phoenix, AZ, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Cuyugan
authors.affiliation: Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Aldrich
authors.affiliation: Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Kurdoglu
authors.affiliation: Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA; Arizona Alzheimer's Consortium, Phoenix, AZ, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Adkins
authors.affiliation: Arizona Alzheimer's Consortium, Phoenix, AZ, USA; Civin Laboratory of Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA.
authors.forename: Geidy
authors.initials: G
authors.lastname: Serrano
authors.affiliation: Arizona Alzheimer's Consortium, Phoenix, AZ, USA; Civin Laboratory of Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.affiliation: Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Craig
authors.affiliation: Arizona Alzheimer's Consortium, Phoenix, AZ, USA; Department of Biochemistry, Midwestern University, Glendale, AZ, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Valla
authors.affiliation: Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA; Arizona Alzheimer's Consortium, Phoenix, AZ, USA; Civin Laboratory of Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA; Banner Alzheimer's Institute, Phoenix, AZ, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.affiliation: Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA; Arizona Alzheimer's Consortium, Phoenix, AZ, USA. Electronic address: wliang@tgen.org.
authors.forename: Winnie S
authors.initials: WS
authors.lastname: Liang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D001253:Astrocytes / Q000276:immunology* / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000276:immunology; D051152:Clusterin / Q000502:physiology; D003176:Complement C3 / Q000502:physiology; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics*; D008297:Male; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D012359:tRNA Methyltransferases / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000944:Antigens, Differentiation, B-Lymphocyte; C038245:C3 protein, human; C495242:CLU protein, human; D051152:Clusterin; D003176:Complement C3; D000949:Histocompatibility Antigens Class II; C045084:invariant chain; D003576:Electron Transport Complex IV; C577147:NDUFA4 protein, human; C577855:Trmt61B protein, human; D012359:tRNA Methyltransferases; C532222:FASTKD2 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Alzheimer's disease; Astrocytes; Immune response; Mitochondria; Posterior cingulate; RNA sequencing