Protective properties of lysozyme on β-amyloid pathology: implications for Alzheimer disease.
The hallmarks of Alzheimer disease are amyloid-β plaques and neurofibrillary tangles accompanied by signs of neuroinflammation. Lysozyme is a major player in the innate immune system and has recently been shown to prevent the aggregation of amyloid-β1-40 in vitro. In this study we found that patients with Alzheimer disease have increased lysozyme levels in the cerebrospinal fluid and lysozyme co-localized with amyloid-β in plaques. In Drosophila neuronal co-expression of lysozyme and amyloid-β1-42 reduced the formation of soluble and insoluble amyloid-β species, prolonged survival and improved the activity of amyloid-β1-42 transgenic flies. This suggests that lysozyme levels rise in Alzheimer disease as a compensatory response to amyloid-β increases and aggregation. In support of this, in vitro aggregation assays revealed that lysozyme associates with amyloid-β1-42 and alters its aggregation pathway to counteract the formation of toxic amyloid-β species. Overall, these studies establish a protective role for lysozyme against amyloid-β associated toxicities and identify increased lysozyme in patients with Alzheimer disease. Therefore, lysozyme has potential as a new biomarker as well as a therapeutic target for Alzheimer disease.
Division of Molecular Biotechnology, Department of Physics, Chemistry and Biology, Linköping University, 581 83 Linköping, Sweden.
Linda
L
Helmfors
Experimental Pathology, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, 581 85 Linköping, Sweden.
Andrea
A
Boman
Experimental Pathology, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, 581 85 Linköping, Sweden.
Livia
L
Civitelli
Experimental Pathology, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, 581 85 Linköping, Sweden.
Sangeeta
S
Nath
Experimental Pathology, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, 581 85 Linköping, Sweden.
Linnea
L
Sandin
Experimental Pathology, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, 581 85 Linköping, Sweden.
Camilla
C
Janefjord
Neuroscience Research Australia and University of New South Wales, Randwick New South Wales 2031, Australia.
Heather
H
McCann
Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgrenska University Hospital, 431 30 Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom.
Henrik
H
Zetterberg
Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgrenska University Hospital, 431 30 Mölndal, Sweden.
Kaj
K
Blennow
Neuroscience Research Australia and University of New South Wales, Randwick New South Wales 2031, Australia.
Glenda
G
Halliday
Division of Molecular Biotechnology, Department of Physics, Chemistry and Biology, Linköping University, 581 83 Linköping, Sweden. Electronic address: ann-christin.brorsson@liu.se.
Ann-Christin
AC
Brorsson
Experimental Pathology, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, 581 85 Linköping, Sweden. Electronic address: katarina.kagedal@liu.se.
Katarina
K
Kågedal
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death; D004331:Drosophila melanogaster; D005260:Female; D006801:Humans; D019476:Insect Proteins / Q000378:metabolism; D008124:Locomotion; D008297:Male; D008875:Middle Aged; D009113:Muramidase / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism* / Q000648:ultrastructure; D058225:Plaque, Amyloid / Q000378:metabolism / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D019476:Insect Proteins; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D009113:Muramidase
Alzheimer disease; Aβ aggregation; Biomarker; Drosophila; Lysozyme