The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide.
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 differe...
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doaj-42b9b2344e1f41cbb83e8af0826989632020-11-25T00:24:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-03-0153e950510.1371/journal.pone.0009505The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide.Stephanie J SosciaJames E KirbyKevin J WashicoskyStephanie M TuckerMartin IngelssonBradley HymanMark A BurtonLee E GoldsteinScott DuongRudolph E TanziRobert D MoirThe 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.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.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.http://europepmc.org/articles/PMC2831066?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Stephanie J Soscia James E Kirby Kevin J Washicosky Stephanie M Tucker Martin Ingelsson Bradley Hyman Mark A Burton Lee E Goldstein Scott Duong Rudolph E Tanzi Robert D Moir |
spellingShingle |
Stephanie J Soscia James E Kirby Kevin J Washicosky Stephanie M Tucker Martin Ingelsson Bradley Hyman Mark A Burton Lee E Goldstein Scott Duong Rudolph E Tanzi Robert D Moir The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS ONE |
author_facet |
Stephanie J Soscia James E Kirby Kevin J Washicosky Stephanie M Tucker Martin Ingelsson Bradley Hyman Mark A Burton Lee E Goldstein Scott Duong Rudolph E Tanzi Robert D Moir |
author_sort |
Stephanie J Soscia |
title |
The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. |
title_short |
The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. |
title_full |
The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. |
title_fullStr |
The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. |
title_full_unstemmed |
The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. |
title_sort |
alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2010-03-01 |
description |
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.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.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. |
url |
http://europepmc.org/articles/PMC2831066?pdf=render |
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