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Research Article

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

  • Stephanie J. Soscia,

    Affiliations: Genetics and Aging Research Unit, Mass General Institute for Neurodegenerative Disease and Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America, Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts, United States of America

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  • James E. Kirby,

    Affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America

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  • Kevin J. Washicosky,

    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

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  • Stephanie M. Tucker,

    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

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  • Martin Ingelsson,

    Affiliation: Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden

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  • Bradley Hyman,

    Affiliations: Genetics and Aging Research Unit, Mass General Institute for Neurodegenerative Disease and Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America, Harvard Medical School, Boston, Massachusetts, United States of America

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  • Mark A. Burton,

    Affiliations: Molecular Aging and Developmental Laboratory, Photonics Center, College of Engineering, Boston University School of Medicine, Boston University, Boston, Massachusetts, United States of America, Boston University Alzheimer's Disease Center, Boston University, Boston, Massachusetts, United States of America

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  • Lee E. Goldstein,

    Affiliations: Molecular Aging and Developmental Laboratory, Photonics Center, College of Engineering, Boston University School of Medicine, Boston University, Boston, Massachusetts, United States of America, Boston University Alzheimer's Disease Center, Boston University, Boston, Massachusetts, United States of America

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  • Scott Duong,

    Affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America

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  • Rudolph E. Tanzi mail,

    tanzi@helix.mgh.harvard.edu

    Affiliations: Genetics and Aging Research Unit, Mass General Institute for Neurodegenerative Disease and Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America, Harvard Medical School, Boston, Massachusetts, United States of America

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  • Robert D. Moir

    Affiliations: Genetics and Aging Research Unit, Mass General Institute for Neurodegenerative Disease and Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America, Harvard Medical School, Boston, Massachusetts, United States of America

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  • Published: March 03, 2010
  • DOI: 10.1371/journal.pone.0009505

Reader Comments (7)

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Immune activation, infection and Alzheimer, further evidence

Posted by Sigrun_Hope on 28 Jun 2010 at 21:22 GMT

The study of Soscia et al documents that Amyloid β-Protein has antimicrobial effect is interesting and the importance of the study are supported by findings of elevated immune activation in Alzheimer`s disease (AD) (1).
In the Soscia study the most pronounced antibiotic effect of Amyloid β-Protein was seen against Candida Albicans. This infective agent is amongst many microbes that elevates activity of the immune mediator tumour necrosis factor-alpha (TNF) (2). It has recently become clear that such immune activation has a general negative impact on cognition (3, 4). Healthy persons with high levels of TNF have elevated risk of developing AD (5) and elevated TNF confers a risk for mild cognitive decline developing into dementia (6). Patients that already have been diagnosed with AD has also have elevated TNF (7). In accordance with these studies of systemic immune activation, post-mortem studies of brain tissue from AD patients show elevated activity in the TNF-pathways (8).

As elevated levels of TNF is associated with negative impact on cognition and confers risk of AD, it has been suggested that antagonizing TNF might be a treatment option (9). Treatment with a TNF-blocking agent has also been tried in an AD patient and were found to have a rapid effect improving some cognitive measures (10). The long term effect of such treatment is uncertain. Importantly, immune suppression is not a good treatment option if the elevated immune activation in is due to an infective agent. In such a case an immune suppressant would make the immune response even more ineffective.
And as mentioned in the comment by Ruth Itzhaki, there are indications that infections elevate the risk of Alzheimer (11-13). It has also been reported that blocking the immune response is associated with more rapid progression in animal models of AD (14, 15).
The fact that Amyloid β-Protein is an antimicrobial peptide supports the hypothesis that immune activation might be caused by subclinical chronic infection. Thus, treatment trials with antibiotic agents might be a better alternative in AD than treatment trials with immune blocking agents.


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No competing interests declared.