title: Decreased plasma iron in Alzheimer's disease is due to transferrin desaturation.
abstract: Plasma iron levels are decreased in Alzheimer's disease (AD) and associated with an idiopathic anemia. We examined iron-binding plasma proteins from AD patients and healthy controls from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing using size exclusion chromatography-inductively coupled plasma-mass spectrometry. Peak area corresponding to transferrin (Tf) saturation was directly compared to routine pathological testing. We found a significant decrease in transferrin-associated iron in AD that was missed by routine pathological tests of transferrin saturation, and that was able to discriminate between AD and controls. The AD cases showed no significant difference in transferrin concentration, only a decrease in total transferrin-bound iron. These findings support that a previously identified decrease in plasma iron levels in AD patients within the AIBL study is attributable to decreased loading of iron into transferrin, and that this subtle but discriminatory change is not observed through routine pathological testing.
authors.affiliation: †Elemental Bio-imaging Facility, University of Technology Sydney, Broadway, New South Wales 2007, Australia.|‡The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3010, Australia.|§Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Hare
authors.affiliation: ∥The Australian eHealth Research Centre, Herston, Queensland 4006, Australia.|⊥CSIRO Preventative Health Flagship, Molecular Science and Engineering, Parkville, Victoria 3052, Australia.
authors.forename: James D
authors.initials: JD
authors.lastname: Doecke
authors.affiliation: ‡The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3010, Australia.|#Cooperative Research Centre for Mental Health, Carlton South, Victoria 3053, Australia.
authors.forename: Noel G
authors.initials: NG
authors.lastname: Faux
authors.affiliation: ‡The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Rembach
authors.affiliation: ‡The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Irene
authors.initials: I
authors.lastname: Volitakis
authors.affiliation: ‡The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3010, Australia.|#Cooperative Research Centre for Mental Health, Carlton South, Victoria 3053, Australia.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fowler
authors.affiliation: ∇Agilent Technologies, Santa Clara, California 95051, United States.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Grimm
authors.affiliation: †Elemental Bio-imaging Facility, University of Technology Sydney, Broadway, New South Wales 2007, Australia.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Doble
authors.affiliation: ‡The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cherny
authors.affiliation: ‡The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: ‡The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.affiliation: ‡The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Blaine R
authors.initials: BR
authors.lastname: Roberts
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D001315:Australia; D016022:Case-Control Studies; D002850:Chromatography, Gel; D005260:Female; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies; D014168:Transferrin / Q000378:metabolism*
chemical_list: D014168:Transferrin; D007501:Iron
keywords: Alzheimer’s disease; iron; size exclusion chromatography-inductively coupled plasma-mass spectrometry; transferrin; transferrin saturation