Protective properties of lysozyme on β-amyloid pathology: implications for Alzheimer disease
2015 (English)In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 83, 122-133 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Elsevier, 2015. Vol. 83, 122-133 p.
Lysozyme, Biomarker, Alzheimer disease, Drosophila, AÎ² aggregation
Cell and Molecular Biology Chemical Sciences
IdentifiersURN: urn:nbn:se:liu:diva-122341DOI: 10.1016/j.nbd.2015.08.024ISI: 000366230000012PubMedID: 26334479OAI: oai:DiVA.org:liu-122341DiVA: diva2:865671