Beneficial effects of increased lysozyme levels in Alzheimer's disease modelled in Drosophila melanogaster

Linnea Sandin, Liza Bergkvist, Sangeeta Nath, Claudia Kielkopf, Camilla Janefjord, Linda Helmfors, Henrik Zetterberg, Kaj Blennow, Hongyun Li, Camilla Nilsberth, Brett Garner, Ann Christin Brorsson, Katarina Kågedal

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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 Aβ1-42 or 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 Aβ1-42 variant with the Arctic gene mutation, lysozyme increased the fly survival and decreased locomotor dysfunction dose dependently. An interaction between lysozyme and Aβ1-42 in 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 Aβ1-42 and 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.

Original languageEnglish
Pages (from-to)3508-3522
Number of pages15
JournalFEBS Journal
DOIs
Publication statusPublished - 01-10-2016

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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