title: Innate phagocytosis by peripheral blood monocytes is altered in Alzheimer's disease.
abstract: Sporadic Alzheimer's disease (AD) is characterised by the deposition and accumulation of specific protein aggregates. Failure of clearance could underlie this process, and recent genetic association studies point towards involvement of the phagocytosis and autophagy pathways. We developed a real-time tri-color flow cytometry method to quantitate the phagocytic function of human peripheral blood monocyte subsets including non-classic CD14(dim)CD16(+), intermediate CD14(+)CD16(+) and classic CD14(+)CD16(-) monocytes. Using this method, we have measured the phagocytic ability of fresh monocytes in a study of preclinical, prodromal and clinical AD, matched with cognitively normal healthy control subjects. Basal levels of phagocytosis in all three subsets of monocytes were similar between healthy controls and AD patients, while a significant increase of basal phagocytosis was found in subjects with high Aβ-amyloid burden as assessed by PET scans. Pre-treating cells with Copaxone (CPX, to stimulate phagocytosis) or ATP (an inhibitor of P2X7-mediated phagocytosis) showed a differential response depending on clinical or Aβ-burden status, indicating a relative functional deficit. Overall the results are consistent with a perturbation of basal and stimulated innate phagocytosis in sporadic AD.
authors.affiliation: The Florey Institute of Neuroscience & Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia. ben.gu@florey.edu.au.
authors.forename: Ben J
authors.identifier: 0000-0001-5500-4453
authors.initials: BJ
authors.lastname: Gu
authors.affiliation: The Florey Institute of Neuroscience & Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: The Florey Institute of Neuroscience & Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
authors.forename: Amber
authors.initials: A
authors.lastname: Ou
authors.affiliation: The Florey Institute of Neuroscience & Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Rembach
authors.affiliation: The Florey Institute of Neuroscience & Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Fowler
authors.affiliation: The Florey Institute of Neuroscience & Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
authors.forename: Pavan K
authors.initials: PK
authors.lastname: Avula
authors.affiliation: The Florey Institute of Neuroscience & Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Horton
authors.affiliation: CSIRO Health and Biosecurity/Australian E-Health Research Centre, Herston, QLD, 4029, Australia.
authors.forename: James D
authors.initials: JD
authors.lastname: Doecke
authors.affiliation: The Florey Institute of Neuroscience & Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.|Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, 3084, Australia.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: CSIRO Health and Biosecurity, Parkville, VIC, 3052, Australia.
authors.forename: S Lance
authors.initials: SL
authors.lastname: Macaulay
authors.affiliation: The Florey Institute of Neuroscience & Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.|Cogstate Pty Ltd, Melbourne, VIC, 3000, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Maruff
authors.affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, 3010, Australia.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Fletcher
authors.affiliation: Centre for Eye Research Australia Royal Victorian Eye and Ear Hospital, The University of Melbourne, East Melbourne, VIC, 3002, Australia.
authors.forename: Robyn
authors.initials: R
authors.lastname: Guymer
authors.affiliation: The Florey Institute of Neuroscience & Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
authors.forename: James S
authors.initials: JS
authors.lastname: Wiley
authors.affiliation: The Florey Institute of Neuroscience & Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, VIC, 3052, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism*; D058227:Amyloidogenic Proteins / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism
chemical_list: D058227:Amyloidogenic Proteins; D017452:Receptors, IgG
keywords: ATP; Alzheimer’s disease; Copaxone (glatiramer acetate); P2X7; Phagocytosis