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dc.contributor.authorSoscia, Stephanie
dc.contributor.authorKirby, James Edward
dc.contributor.authorWashicosky, Kevin J.
dc.contributor.authorTucker, Stephanie
dc.contributor.authorIngelsson, Martin
dc.contributor.authorHyman, Bradley Theodore
dc.contributor.authorBurton, Mark A.
dc.contributor.authorDuong, Scott
dc.contributor.authorTanzi, Rudolph Emile
dc.contributor.authorMoir, Robert D.
dc.contributor.authorGoldstein, Lee E.
dc.date.accessioned2012-12-10T19:04:33Z
dc.date.issued2010
dc.identifier.citationSoscia, Stephanie J., James E. Kirby, Kevin J. Washicosky, Stephanie M. Tucker, Martin Ingelsson, Bradley Hyman, Mark A. Burton, et. al. 2010. The Alzheimer's disease-associated amyloid \(\beta\)-protein is an antimicrobial peptide. PLoS ONE 5(3): e9505.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10021559
dc.description.abstractBackground: 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.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi://10.1371/journal.pone.0009505en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831066/pdf/en_US
dash.licenseLAA
dc.subjectimmunologyen_US
dc.subjectmicrobiologyen_US
dc.subjectinnate immunityen_US
dc.subjectneurological disordersen_US
dc.subjectAlzheimer's diseaseen_US
dc.titleThe Alzheimer's Disease-Associated Amyloid \(\beta\)-Protein Is an Antimicrobial Peptideen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorMoir, Robert D.
dc.date.available2012-12-10T19:04:33Z
dash.affiliation.otherHMS^Neurology-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Neurology-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Neurology-Massachusetts General Hospitalen_US
dc.identifier.doi10.1371/journal.pone.0009505*
dash.authorsorderedfalse
dash.contributor.affiliatedKirby, James
dash.contributor.affiliatedMoir, Robert
dash.contributor.affiliatedTanzi, Rudolph
dash.contributor.affiliatedHyman, Bradley


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