The Alzheimer's Disease-Associated Amyloid beta-Protein Is an Antimicrobial Peptide
2010 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 5, no 3, e9505- p.Article in journal (Refereed) Published
Background: The amyloid beta-protein (A beta) is believed to be the key mediator of Alzheimer's disease (AD) pathology. A beta is most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, A beta has been shown to be a specific ligand for a number of different receptors and other molecules, transported by complex trafficking pathways, modulated in response to a variety of environmental stressors, and able to induce pro-inflammatory activities. Methodology/Principal Findings: Here, we provide data supporting an in vivo function for A beta as an antimicrobial peptide (AMP). Experiments used established in vitro assays to compare antimicrobial activities of A beta and LL-37, an archetypical human AMP. Findings reveal that A beta exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37. Furthermore, we show that AD whole brain homogenates have significantly higher antimicrobial activity than aged matched non-AD samples and that AMP action correlates with tissue A beta levels. Consistent with A beta-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-A beta antibodies. Conclusions/Significance: Our findings suggest A beta is a hitherto unrecognized AMP that may normally function in the innate immune system. This finding stands in stark contrast to current models of A beta-mediated pathology and has important implications for ongoing and future AD treatment strategies.
Place, publisher, year, edition, pages
2010. Vol. 5, no 3, e9505- p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-136953DOI: 10.1371/journal.pone.0009505ISI: 000275063400012PubMedID: 20209079OAI: oai:DiVA.org:uu-136953DiVA: diva2:377861