dc.contributor.author | Soscia, Stephanie | |
dc.contributor.author | Kirby, James Edward | |
dc.contributor.author | Washicosky, Kevin J. | |
dc.contributor.author | Tucker, Stephanie | |
dc.contributor.author | Ingelsson, Martin | |
dc.contributor.author | Hyman, Bradley Theodore | |
dc.contributor.author | Burton, Mark A. | |
dc.contributor.author | Duong, Scott | |
dc.contributor.author | Tanzi, Rudolph Emile | |
dc.contributor.author | Moir, Robert D. | |
dc.contributor.author | Goldstein, Lee E. | |
dc.date.accessioned | 2012-12-10T19:04:33Z | |
dc.date.issued | 2010 | |
dc.identifier.citation | Soscia, 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.issn | 1932-6203 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:10021559 | |
dc.description.abstract | 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. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | doi://10.1371/journal.pone.0009505 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831066/pdf/ | en_US |
dash.license | LAA | |
dc.subject | immunology | en_US |
dc.subject | microbiology | en_US |
dc.subject | innate immunity | en_US |
dc.subject | neurological disorders | en_US |
dc.subject | Alzheimer's disease | en_US |
dc.title | The Alzheimer's Disease-Associated Amyloid \(\beta\)-Protein Is an Antimicrobial Peptide | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | PLoS ONE | en_US |
dash.depositing.author | Moir, Robert D. | |
dc.date.available | 2012-12-10T19:04:33Z | |
dash.affiliation.other | HMS^Neurology-Massachusetts General Hospital | en_US |
dash.affiliation.other | HMS^Neurology-Massachusetts General Hospital | en_US |
dash.affiliation.other | HMS^Neurology-Massachusetts General Hospital | en_US |
dc.identifier.doi | 10.1371/journal.pone.0009505 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Kirby, James | |
dash.contributor.affiliated | Hyman, Bradley | |
dash.contributor.affiliated | Moir, Robert | |
dash.contributor.affiliated | Tanzi, Rudolph | |