The Alzheimer’s Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide

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The Alzheimer’s Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide

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Title: The Alzheimer’s Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide
Author: Washicosky, Kevin J.; Tucker, Stephanie M.; Ingelsson, Martin; Burton, Mark A.; Duong, Scott; Kirby, James Edward; Hyman, Bradley Theodore; Goldstein, Lee E.; Tanzi, Rudolph Emile; Moir, Robert D.

Note: Order does not necessarily reflect citation order of authors.

Citation: Soscia, Stephanie J., James E. Kirby, Kevin J. Washicosky, Stephanie M. Tucker, Martin Ingelsson, Bradley Hyman, Mark A. Burton, Lee E. Goldstein, Scott Duong, Rudolph E. Tanzi, and Robert D. Moir. 2010. The Alzheimer's disease-associated amyloid β-protein is an antimicrobial peptide. PLoS ONE 5, no. 3: e9505.
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Abstract: Background: The amyloid β-protein (Aβ) is believed to be the key mediator of Alzheimer's disease (AD) pathology. Aβ is most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, Aβ 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 Aβ as an antimicrobial peptide (AMP). Experiments used established in vitro assays to compare antimicrobial activities of Aβ and LL-37, an archetypical human AMP. Findings reveal that Aβ 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 Aβ levels. Consistent with Aβ-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-Aβ antibodies. Conclusions/Significance: Our findings suggest Aβ is a hitherto unrecognized AMP that may normally function in the innate immune system. This finding stands in stark contrast to current models of Aβ-mediated pathology and has important implications for ongoing and future AD treatment strategies.
Published Version: doi://10.1371/journal.pone.0009505
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831066/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:8160863

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