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dc.contributor.authorKumar, Deepak
dc.contributor.authorChoi, Se Hoon
dc.contributor.authorWashicosky, Kevin J.
dc.contributor.authorEimer, William
dc.contributor.authorTucker, Stephanie Catherine
dc.contributor.authorGhofrani, Jessica
dc.contributor.authorLefkowitz, Aaron
dc.contributor.authorMcColl, Gawain
dc.contributor.authorGoldstein, Lee E.
dc.contributor.authorTanzi, Rudolph Emile
dc.contributor.authorMoir, Robert D.
dc.date.accessioned2017-03-09T19:33:16Z
dc.date.issued2016
dc.identifier.citationKumar, D. K. V., S. H. Choi, K. J. Washicosky, W. A. Eimer, S. Tucker, J. Ghofrani, A. Lefkowitz, et al. 2016. “Amyloid-β Peptide Protects Against Microbial Infection in Mouse and Worm Models of Alzheimers Disease.” Science Translational Medicine 8 (340) (May 25): 340ra72–340ra72. doi:10.1126/scitranslmed.aaf1059.en_US
dc.identifier.issn1946-6234en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:30754357
dc.description.abstractThe amyloid-β peptide (Aβ) is a key protein in Alzheimer's disease (AD) pathology. We previously reported in vitro evidence suggesting Aβ is an antimicrobial peptide. Here we provide the first in vivo evidence showing high Aβ production protects against fungal and bacterial infections in mouse and nematode AD models. In Aβ-null mouse models low Aβ production is associated with attenuated resistance to infection. Regarding mechanism, we show Aβ oligomerization, a behavior traditionally viewed as intrinsically pathological, is necessary for the antimicrobial activities of the peptide. Soluble Aβ oligomers bind microbial cell walls, developing protofibrils inhibit pathogen host cell adhesion, and, finally, proteaseresistant β-amyloid fibrils agglutinate and entrap the invading microbes. We also show that infection of 5XFAD mouse brain with S. Typhimurium bacteria rapidly seeds and dramatically accelerates β-amyloid deposition, which closely co-localizes with invading bacteria. Collectively, our findings raise the intriguing possibility that β-amyloid plays a protective role in innate immunity and infectious or sterile inflammatory stimuli may drive amyloidosis. These data suggest a dual protective/damaging role for Aβ, as has been described for other antimicrobial peptides.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Association for the Advancement of Science (AAAS)en_US
dc.relation.isversionof10.1126/scitranslmed.aaf1059en_US
dash.licenseLAA
dc.titleAmyloid-β Protein Protects Against Microbial Infection In Transgenic C. elegans and 5XFAD Miceen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalScience Translational Medicineen_US
dash.depositing.authorMoir, Robert D.
dash.waiver2016-02-04
dc.date.available2017-03-09T19:33:16Z
dc.identifier.doi10.1126/scitranslmed.aaf1059*
dash.authorsorderedfalse
dash.contributor.affiliatedEimer, William
dash.contributor.affiliatedTucker, Stephanie Catherine
dash.contributor.affiliatedKumar, Deepak
dash.contributor.affiliatedMoir, Robert
dash.contributor.affiliatedChoi, Se Hoon
dash.contributor.affiliatedTanzi, Rudolph


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