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The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide.

Authors: Soscia, SJ  Kirby, JE  Washicosky, KJ  Tucker, SM  Ingelsson, M  Hyman, B  Burton, MA  Goldstein, LE  Duong, S  Tanzi, RE  Moir, RD 
Citation: Soscia SJ, etal., PLoS One. 2010 Mar 3;5(3):e9505. doi: 10.1371/journal.pone.0009505.
Pubmed: (View Article at PubMed) PMID:20209079
DOI: Full-text: DOI:10.1371/journal.pone.0009505

BACKGROUND: The amyloid beta-protein (Abeta) is believed to be the key mediator of Alzheimer's disease (AD) pathology. Abeta is most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, Abeta 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 Abeta as an antimicrobial peptide (AMP). Experiments used established in vitro assays to compare antimicrobial activities of Abeta and LL-37, an archetypical human AMP. Findings reveal that Abeta 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 Abeta levels. Consistent with Abeta-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-Abeta antibodies. CONCLUSIONS/SIGNIFICANCE: Our findings suggest Abeta is a hitherto unrecognized AMP that may normally function in the innate immune system. This finding stands in stark contrast to current models of Abeta-mediated pathology and has important implications for ongoing and future AD treatment strategies.

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CRRD ID: 10400853
Created: 2015-09-19
Species: All species
Last Modified: 2015-09-19
Status: ACTIVE



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