title: Upregulation of glycolytic enzymes, mitochondrial dysfunction and increased cytotoxicity in glial cells treated with Alzheimer's disease plasma.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder associated with increased oxidative stress and neuroinflammation. Markers of increased protein, lipid and nucleic acid oxidation and reduced activities of antioxidant enzymes have been reported in AD plasma. Amyloid plaques in the AD brain elicit a range of reactive inflammatory responses including complement activation and acute phase reactions, which may also be reflected in plasma. Previous studies have shown that human AD plasma may be cytotoxic to cultured cells. We investigated the effect of pooled plasma (n = 20 each) from healthy controls, individuals with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) on cultured microglial cells. AD plasma and was found to significantly decrease cell viability and increase glycolytic flux in microglia compared to plasma from healthy controls. This effect was prevented by the heat inactivation of complement. Proteomic methods and isobaric tags (iTRAQ) found the expression level of complement and other acute phase proteins to be altered in MCI and AD plasma and an upregulation of key enzymes involved in the glycolysis pathway in cells exposed to AD plasma. Altered expression levels of acute phase reactants in AD plasma may alter the energy metabolism of glia.
authors.affiliation: Bioanalytical Mass Spectrometry Facility, MW Analytical Centre, University of New South Wales, Sydney, Australia; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Tharusha
authors.initials: T
authors.lastname: Jayasena
authors.affiliation: Bioanalytical Mass Spectrometry Facility, MW Analytical Centre, University of New South Wales, Sydney, Australia; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia; School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Poljak
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Nady
authors.initials: N
authors.lastname: Braidy
authors.affiliation: Bioanalytical Mass Spectrometry Facility, MW Analytical Centre, University of New South Wales, Sydney, Australia; School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: George
authors.initials: G
authors.lastname: Smythe
authors.affiliation: Bioanalytical Mass Spectrometry Facility, MW Analytical Centre, University of New South Wales, Sydney, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Raftery
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Hill
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia; Dementia Collaborative Research Centre, University of New South Wales, Sydney, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Brodaty
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia; Neuropsychiatric Institute, the Prince of Wales Hospital, Sydney, Australia.
authors.forename: Julian
authors.initials: J
authors.lastname: Trollor
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia; Neuropsychiatric Institute, the Prince of Wales Hospital, Sydney, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kochan
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia; Neuropsychiatric Institute, the Prince of Wales Hospital, Sydney, Australia.
authors.forename: Perminder
authors.initials: P
authors.lastname: Sachdev
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000473:pathology; D002461:Cell Line, Transformed; D005260:Female; D006019:Glycolysis; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology* / Q000473:pathology; D009457:Neuroglia / Q000201:enzymology* / Q000473:pathology; D010949:Plasma