The Alzheimer's Disease-Associated Amyloid \(\beta\)-Protein Is an Antimicrobial Peptide
Washicosky, Kevin J.
Burton, Mark A.
Goldstein, Lee E.Note: Order does not necessarily reflect citation order of authors.
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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.
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.
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