Alzheimer's disease is associated with altered expression of genes involved in immune response and mitochondrial processes in astrocytes
NEUROBIOLOGY OF AGING
Authors: Sekar, Shobana; McDonald, Jacquelyn; Cuyugan, Lori; Aldrich, Jessica; Kurdoglu, Ahmet; Adkins, Jonathan; Serrano, Geidy; Beach, Thomas G.; Craig, David W.; Valla, Jonathan; Reiman, Eric M.; Liang, Winnie S.
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 APOEe4 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. (C) 2015 The Authors. Published by Elsevier Inc.
In Vitro Salivary Protein Adsorption Profile on Titanium and Ceramic Surfaces and the Corresponding Putative Immunological Implications
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Authors: Wei, Chen-Xuan .; Burrow, Michael Francis; Botelho, Michael George; Lam, Henry; Leung, Wai Keung
Abstract
Immune responses triggered by implant abutment surfaces contributed by surface-adsorbed proteins are critical in clinical implant integration. How material surface-adsorbed proteins relate to host immune responses remain unclear. This study aimed to profile and address the immunological roles of surface-adsorbed salivary proteins on conventional implant abutment materials. Standardized polished bocks (5 x 5 x 1 mm(3)) were prepared from titanium and feldspathic ceramic. Salivary acquired pellicle formed in vitro was examined by liquid chromatography-tandem mass spectrometry and gene ontology (GO) analysis to identify and characterize the adsorbed proteins. Out of 759 proteins identified from pooled saliva samples, 396 were found to be attached to the two materials tested-369 on titanium and 298 on ceramic, with 281 common to both. GO annotation of immune processes was undertaken to form a protein-protein interaction network, and 14 hub proteins (>= 6 interaction partners) (coding genes: B2M, C3, CLU, DEFA1, HSP90AA1, HSP90AB1, LTF, PIGR, PSMA2, RAC1, RAP1A, S100A8, S100A9, and SLP1) were identified as the key proteins connecting multiple (6-9) immune processes. The results offered putative immunological prospects of implant abutment material surface-adsorbed salivary proteins, which could potentially underpin the dynamic nature of implant-mucosal/implant-microbial interactions.