title: Gene Expression of Quaking in Sporadic Alzheimer's Disease Patients is Both Upregulated and Related to Expression Levels of Genes Involved in Amyloid Plaque and Neurofibrillary Tangle Formation.
abstract: Quaking (QKI) is a gene exclusively expressed within glial cells. QKI has previously been implicated in various neurological disorders and diseases, including Alzheimer's disease (AD), a condition for which increasing evidence suggests a central role of glia cells. The objective of the present study was to investigate the expression levels of QKI and three QKI isoforms (QKI5, QKI6, and QKI7) in AD. Genes that have previously been related to the ontogeny and progression of AD, specifically APP, PSEN1, PSEN2, and MAPT, were also investigated. A real-time PCR assay of 123 samples from human postmortem sporadic AD patients and control brains was performed. The expression values were analyzed with an analysis of covariance model and subsequent multiple regressions to explore the possibility of related expression values between QKI, QKI isoforms, and AD-related genes. Further, the sequences of AD-related genes were analyzed for the presence of QKI binding domains. QKI and all measured QKI isoforms were found to be significantly upregulated in AD samples, relative to control samples. However, APP, PSEN1, PSEN2, and MAPT were not found to be significantly different. QKI and QKI isoforms were found to be predictive for the variance of APP, PSEN1, PSEN2, and MAPT, and putative QKI binding sites suggests an interaction with QKI. Overall, these results implicate a possible role of QKI in AD, although the exact mechanism by which this occurs remains to be uncovered.
authors.affiliation: Department of Evolution and Development, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Bryn
authors.initials: B
authors.lastname: Farnsworth
authors.affiliation: Department of Neuroscience, Uppsala Biomedical Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Christiane
authors.initials: C
authors.lastname: Peuckert
authors.affiliation: Department of Evolution and Development, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Bettina
authors.initials: B
authors.lastname: Zimmermann
authors.affiliation: Department of Evolution and Development, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Elena
authors.initials: E
authors.lastname: Jazin
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of Neuropathology, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Petronella
authors.initials: P
authors.lastname: Kettunen
authors.affiliation: Department of Evolution and Development, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Lina Sors
authors.initials: LS
authors.lastname: Emilsson
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D009154:Mutation / Q000235:genetics; D016874:Neurofibrillary Tangles / Q000235:genetics*; D058225:Plaque, Amyloid / Q000235:genetics*; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D053766:Presenilin-2 / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D020033:Protein Isoforms; C490832:QKI protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D016875:tau Proteins
keywords: APP; Amyloid-β; MAPT; PSEN1; PSEN2; gene expression; glia; neurodegenerative diseases; real-time polymerase chain reaction