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Alzheimer’s Disease-Associated β-amyloid Is Rapidly Seeded by herpesviridae to Protect Against Brain Infection

41 Pages Posted: 5 Apr 2018   Sneak Peek Status: Review Complete

William A. Eimer

Harvard University - Genetics and Aging Research Unit

Deepak Kumar Vijaya Kumar

Harvard University - Genetics and Aging Research Unit

Nanda Kumar N. Shanmugam

Harvard University - Genetics and Aging Research Unit

Kevin J. Washicosky

Harvard University - Genetics and Aging Research Unit

Alex S. Rodriguez

Harvard University - Department of Neurology

Bence György

Harvard University - Department of Neurology

Xandra O. Breakefield

Harvard University - Department of Neurology

Rudolph E. Tanzi

Harvard University - Genetics and Aging Research Unit

Robert D. Moir

Harvard University - Genetics and Aging Research Unit

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Abstract

Amyloid-β peptide (Aβ) fibrilization and deposition as β-amyloid is a hallmark Alzheimer's disease (AD) pathology. We recently reported Aβ is an innate immune protein and the peptides expression protects against fungal and bacterial infections in animal and cell culture models, doubling host survival in some cases. However, fibrilization pathways mediate Aβ's antimicrobial activities. Thus, infection can dramatically accelerate β- amyloid deposition. Here, we show herpesvirus glycoprotein B binding induces Aβ fibrillization, mediating protective activities against neurotropic herpes simplex virus 1 (HSV1) and human herpesvirus 6 (HHV6). Moreover, herpesviridae infection rapidly seed plaque deposition in 5XFAD mice and 3-dimensional human neural cell cultures. The accompanying paper by Readhead et al. show AD progression correlates with increased abundance of HSV1, HHV6, and herpesvirus 7 across multiple brain regions. Our findings, together with those of Readhead et al., provide a novel etiological mechanism for AD, in which infection with herpesviridae may promote Aβ-amyloidosis.

Suggested Citation

Eimer, William A. and Vijaya Kumar, Deepak Kumar and Shanmugam, Nanda Kumar N. and Washicosky, Kevin J. and Rodriguez, Alex S. and György, Bence and Breakefield, Xandra O. and Tanzi, Rudolph E. and Moir, Robert D., Alzheimer’s Disease-Associated β-amyloid Is Rapidly Seeded by herpesviridae to Protect Against Brain Infection (April 2017). Available at SSRN: https://ssrn.com/abstract=3155923 or http://dx.doi.org/10.2139/ssrn.3155923
This is a paper under consideration at Cell Press and has not been peer-reviewed.

William A. Eimer

Harvard University - Genetics and Aging Research Unit

Charlestown, MA
United States

Deepak Kumar Vijaya Kumar

Harvard University - Genetics and Aging Research Unit

Charlestown, MA
United States

Nanda Kumar N. Shanmugam

Harvard University - Genetics and Aging Research Unit

Charlestown, MA
United States

Kevin J. Washicosky

Harvard University - Genetics and Aging Research Unit

Charlestown, MA
United States

Alex S. Rodriguez

Harvard University - Department of Neurology

15 Parkman Street
Wang Ambulatory Care Center, 8th Floor, Suite 835
Boston, MA 02114
United States

Bence György

Harvard University - Department of Neurology

15 Parkman Street
Wang Ambulatory Care Center, 8th Floor, Suite 835
Boston, MA 02114
United States

Xandra O. Breakefield

Harvard University - Department of Neurology

15 Parkman Street
Wang Ambulatory Care Center, 8th Floor, Suite 835
Boston, MA 02114
United States

Rudolph E. Tanzi (Contact Author)

Harvard University - Genetics and Aging Research Unit ( email )

Charlestown, MA
United States

Robert D. Moir

Harvard University - Genetics and Aging Research Unit ( email )

Charlestown, MA
United States