title: The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Genetics and Aging Research Unit, Mass General Institute for Neurodegenerative Disease and Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Soscia
authors.forename: James E
authors.initials: JE
authors.lastname: Kirby
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Washicosky
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Tucker
authors.forename: Martin
authors.initials: M
authors.lastname: Ingelsson
authors.forename: Bradley
authors.initials: B
authors.lastname: Hyman
authors.forename: Mark A
authors.initials: MA
authors.lastname: Burton
authors.forename: Lee E
authors.initials: LE
authors.lastname: Goldstein
authors.forename: Scott
authors.initials: S
authors.lastname: Duong
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: Robert D
authors.initials: RD
authors.lastname: Moir
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000502:physiology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001921:Brain / Q000473:pathology; D002176:Candida albicans / Q000378:metabolism; D002470:Cell Survival; D004777:Environment; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D008024:Ligands; D008826:Microbial Sensitivity Tests; D010078:Oxazines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry; D014966:Xanthenes / Q000494:pharmacology; D054804:Cathelicidins
chemical_list: D016229:Amyloid beta-Peptides; D023181:Antimicrobial Cationic Peptides; D008024:Ligands; D010078:Oxazines; D011994:Recombinant Proteins; D014966:Xanthenes; C005843:resazurin; D054804:Cathelicidins