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

By Stephanie J. Soscia, J. Kirby, Kevin J. Washicosky, S. Tucker, M. Ingelsson, Bradley T. Hyman, M. Burton, L. Goldstein, S. Duong, Rudolph E. Tanzi and 1 more. PLoS ONE, 2010

928 citations recorded by the source corpus.

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.

Subfields: Microbiology, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/700647dcb83232889b4e2f7006386409c4693eb1

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Citations in the corpus

Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019, neutral): “Synthetic and AD-brain derived Aβ peptide fibrils significantly inhibit the growth of gram positive and gram negative bacteria, fungus (Soscia et al., 2010) and herpesvirus, and inhibits the entry of herpesvirus into cells (Bourgade et al.”
The genetics of Alzheimer disease. (2012, background): “Interestingly, the innate immune system has recently gained increased attention in AD, with our discovery that Ab may act as an antimicrobial peptide in the brain’s innate immune system (Soscia et al. 2010).”
The genetics of Alzheimer disease: back to the future. (2010, background): “In this context it is interesting to note recent data suggesting that Ab could function as an antimicrobial peptide that may have a normal function in the innate immune system (Soscia et al., 2010).”