title: Quantitative proteomics of delirium cerebrospinal fluid.
abstract: Delirium is a common cause and complication of hospitalization in older people, being associated with higher risk of future dementia and progression of existing dementia. However relatively little data are available on which biochemical pathways are dysregulated in the brain during delirium episodes, whether there are protein expression changes common among delirium subjects and whether there are any changes which correlate with the severity of delirium. We now present the first proteomic analysis of delirium cerebrospinal fluid (CSF), and one of few studies exploring protein expression changes in delirium. More than 270 proteins were identified in two delirium cohorts, 16 of which were dysregulated in at least 8 of 17 delirium subjects compared with a mild Alzheimer's disease neurological control group, and 31 proteins were significantly correlated with cognitive scores (mini-mental state exam and acute physiology and chronic health evaluation III). Bioinformatics analyses revealed expression changes in several protein family groups, including apolipoproteins, secretogranins/chromogranins, clotting/fibrinolysis factors, serine protease inhibitors and acute-phase response elements. These data not only provide confirmatory evidence that the inflammatory response is a component of delirium, but also reveal dysregulation of protein expression in a number of novel and unexpected clusters of proteins, in particular the granins. Another surprising outcome of this work is the level of similarity of CSF protein profiles in delirium patients, given the diversity of causes of this syndrome. These data provide additional elements for consideration in the pathophysiology of delirium as well as potential biomarker candidates for delirium diagnosis.
authors.affiliation: 1] Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, NSW, Australia [2] School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia [3] Center for Healthy Brain Ageing, University of New South Wales, Sydney, NSW, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Poljak
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Hill
authors.affiliation: Edinburgh Delirium Research Group, University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Hall
authors.affiliation: Edinburgh Delirium Research Group, University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: MacLullich
authors.affiliation: Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, NSW, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Raftery
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Tai
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Yan
authors.affiliation: 1] Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia [2] Department of Geriatric Medicine, Prince of Wales Hospital, Sydney, NSW, Australia.
authors.forename: G A
authors.initials: GA
authors.lastname: Caplan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D003693:Delirium / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008297:Male; D040901:Proteomics / Q000379:methods*
chemical_list: D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins