Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease

Deepak Kumar Vijaya Kumar; Se Hoon Choi; Kevin J. Washicosky; William A. Eimer; Stephanie Tucker; Jessica Ghofrani; Aaron Lefkowitz; Gawain McColl; Lee E. Goldstein; Rudolph E. Tanzi; Robert D. Moir

doi:10.1126/scitranslmed.aaf1059

Research ArticleAlzheimer’s Disease

Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease

Deepak Kumar Vijaya Kumar¹,*,
Se Hoon Choi¹,*,
Kevin J. Washicosky¹,*,
William A. Eimer¹,
Stephanie Tucker¹,
Jessica Ghofrani¹,
Aaron Lefkowitz¹,
Gawain McColl²,
Lee E. Goldstein³,
Rudolph E. Tanzi¹,† and
Robert D. Moir¹,†

¹Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
²The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3052, Australia.
³Department of Psychiatry, Boston University, Boston, MA 02215, USA.

↵†Corresponding author. Email: moir{at}helix.mgh.harvard.edu (R.D.M.); tanzi{at}helix.mgh.harvard.edu (R.E.T.)

↵* These authors contributed equally to this work.

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Science Translational Medicine 25 May 2016:
Vol. 8, Issue 340, pp. 340ra72
DOI: 10.1126/scitranslmed.aaf1059

Deepak Kumar Vijaya Kumar

1Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

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Se Hoon Choi

1Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

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Kevin J. Washicosky

1Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

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William A. Eimer

1Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

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Stephanie Tucker

1Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

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Jessica Ghofrani

1Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

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Aaron Lefkowitz

1Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

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Gawain McColl

2The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3052, Australia.

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Lee E. Goldstein

3Department of Psychiatry, Boston University, Boston, MA 02215, USA.

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Rudolph E. Tanzi

1Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

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For correspondence: moir@helix.mgh.harvard.edu tanzi@helix.mgh.harvard.edu

Robert D. Moir

1Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

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For correspondence: moir@helix.mgh.harvard.edu tanzi@helix.mgh.harvard.edu

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Rehabilitation of a β-amyloid bad boy

A protein called Aβ is thought to cause neuronal death in Alzheimer’s disease (AD). Aβ forms insoluble aggregates in the brains of patients with AD, which are a hallmark of the disease. Aβ and its propensity for aggregation are widely viewed as intrinsically abnormal. However, in new work, Kumar et al. show that Aβ is a natural antibiotic that protects the brain from infection. Most surprisingly, Aβ aggregates trap and imprison bacterial pathogens. It remains unclear whether Aβ is fighting a real or falsely perceived infection in AD. However, in any case, these findings identify inflammatory pathways as potential new drug targets for treating AD.

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β-Amyloid protein oligomerization and fibrillization, known to be pathogenic in Alzheimer’s disease, may play a physiological role in microbial entrapment and innate immunity.

Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease

Rehabilitation of a β-amyloid bad boy

Science Translational Medicine

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