title: Beneficial effects of increased lysozyme levels in Alzheimer's disease modelled in Drosophila melanogaster.
abstract: Genetic polymorphisms of immune genes that associate with higher risk to develop Alzheimer's disease (AD) have led to an increased research interest on the involvement of the immune system in AD pathogenesis. A link between amyloid pathology and immune gene expression was suggested in a genome-wide gene expression study of transgenic amyloid mouse models. In this study, the gene expression of lysozyme, a major player in the innate immune system, was found to be increased in a comparable pattern as the amyloid pathology developed in transgenic mouse models of AD. A similar pattern was seen at protein levels of lysozyme in human AD brain and CSF, but this lysozyme pattern was not seen in a tau transgenic mouse model. Lysozyme was demonstrated to be beneficial for different Drosophila melanogaster models of AD. In flies that expressed Aβ1-42or AβPP together with BACE1 in the eyes, the rough eye phenotype indicative of toxicity was completely rescued by coexpression of lysozyme. In Drosophila flies bearing the Aβ1-42variant with the Arctic gene mutation, lysozyme increased the fly survival and decreased locomotor dysfunction dose dependently. An interaction between lysozyme and Aβ1-42in the Drosophila eye was discovered. We propose that the increased levels of lysozyme, seen in mouse models of AD and in human AD cases, were triggered by Aβ1-42and caused a beneficial effect by binding of lysozyme to toxic species of Aβ1-42, which prevented these from exerting their toxic effects. These results emphasize the possibility of lysozyme as biomarker and therapeutic target for AD.
authors: Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Sweden.
authors: Linnea
authors: L
authors: Sandin
authors: Division of Molecular Biotechnology, Department of Physics, Chemistry and Biology, Linköping University, Sweden.
authors: Liza
authors: L
authors: Bergkvist
authors: Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Sweden.
authors: Sangeeta
authors: S
authors: Nath
authors: Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Sweden.
authors: Claudia
authors: C
authors: Kielkopf
authors: Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Sweden.
authors: Camilla
authors: C
authors: Janefjord
authors: Division of Molecular Biotechnology, Department of Physics, Chemistry and Biology, Linköping University, Sweden.
authors: Linda
authors: L
authors: Helmfors
authors: Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden.|UCL Institute of Neurology, London, UK.
authors: Henrik
authors: H
authors: Zetterberg
authors: Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden.
authors: Kaj
authors: K
authors: Blennow
authors: Illawarra Health and Medical Research Institute, University of Wollongong, Australia.
authors: Hongyun
authors: H
authors: Li
authors: Department of Acute Internal Medicine and Geriatrics and Department of Clinical and Experimental Medicine, Linköping University, Sweden.
authors: Camilla
authors: C
authors: Nilsberth
authors: Illawarra Health and Medical Research Institute, University of Wollongong, Australia.|School of Biological Sciences, University of Wollongong, Australia.
authors: Brett
authors: B
authors: Garner
authors: Division of Molecular Biotechnology, Department of Physics, Chemistry and Biology, Linköping University, Sweden. ann-christin.brorsson@liu.se.
authors: Ann-Christin
authors: AC
authors: Brorsson
authors: Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Sweden. katarina.kagedal@liu.se.
authors: Katarina
authors: K
authors: Kågedal
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D005123:Eye / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012333:RNA, Messenger; C075222:amyloid beta-protein (1-42); D009113:Muramidase
keywords: 
  Drosophila
  ; Alzheimer's disease; amyloid-β; lysozyme