RGD Reference Report - The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. - Rat Genome Database

RGD Reference Report - The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. - Rat Genome Database

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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.
RGD ID:	10400853
Pubmed:	PMID:20209079 (View Abstract at PubMed)
PMCID:	PMC2831066 (View Article at PubMed Central)
DOI:	DOI:10.1371/journal.pone.0009505 (Journal Full-text)
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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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
App	Rat	antibacterial humoral response	involved_in	IDA		PMID:20209079	UniProt
App	Rat	antifungal humoral response	involved_in	IDA		PMID:20209079	UniProt
App	Rat	antimicrobial humoral immune response mediated by antimicrobial peptide	involved_in	IDA		PMID:20209079	UniProt
App	Rat	defense response to Gram-negative bacterium	involved_in	IDA		PMID:20209079	UniProt
App	Rat	defense response to Gram-positive bacterium	involved_in	IDA		PMID:20209079	UniProt
App	Rat	innate immune response	involved_in	IDA		PMID:20209079	UniProt
App	Rat	response to yeast	involved_in	IDA		PMID:20209079	UniProt

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Genes (Rattus norvegicus)

App (amyloid beta precursor protein)

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