Human Herpesvirus 6 Detection in Alzheimer's Disease Cases and Controls across Multiple Cohorts

Mary Alice Allnutt; Kory Johnson; David A Bennett; Sarah M Connor; Juan C Troncoso; Olga Pletnikova; Marilyn S Albert; Susan M Resnick; Sonja W Scholz; Philip L De Jager; Steven Jacobson

doi:10.1016/j.neuron.2019.12.031

Human Herpesvirus 6 Detection in Alzheimer's Disease Cases and Controls across Multiple Cohorts

Neuron. 2020 Mar 18;105(6):1027-1035.e2. doi: 10.1016/j.neuron.2019.12.031. Epub 2020 Jan 23.

Authors

Affiliations

¹ Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA.
² Bioinformatics Section, Information Technology & Bioinformatics Program, Division of Intramural Research (DIR), National Institute of Neurological Disorders and Stroke/National Institute of Health, Bethesda, MD 20814, USA.
³ Alzheimer Disease Center, RUSH University, Chicago, IL 60612, USA.
⁴ Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
⁵ Department of Pathology (Neuropathology), Johns Hopkins University Medical Center, Baltimore, MD 21205, USA.
⁶ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁷ Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
⁸ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA.
⁹ Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA. Electronic address: jacobsons@ninds.nih.gov.

Abstract

The interplay between viral infection and Alzheimer's disease (AD) has long been an area of interest, but proving causality has been elusive. Several recent studies have renewed the debate concerning the role of herpesviruses, and human herpesvirus 6 (HHV-6) in particular, in AD. We screened for HHV-6 detection across three independent AD brain repositories using (1) RNA sequencing (RNA-seq) datasets and (2) DNA samples extracted from AD and non-AD control brains. The RNA-seq data were screened for pathogens against taxon references from over 25,000 microbes, including 118 human viruses, whereas DNA samples were probed for PCR reactivity to HHV-6A and HHV-6B. HHV-6 demonstrated little specificity to AD brains over controls by either method, whereas other viruses, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), were detected at comparable levels. These direct methods of viral detection do not suggest an association between HHV-6 and AD.

Keywords: Alzheimer’s disease; herpesvirus; human herpesvirus 6.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Alzheimer Disease / virology*
Brain / virology*
Case-Control Studies
Cohort Studies
Female
Herpesvirus 6, Human / genetics
Herpesvirus 6, Human / isolation & purification*
Humans
Male
Sequence Analysis, DNA / statistics & numerical data
Sequence Analysis, RNA / statistics & numerical data

Abstract

Publication types

MeSH terms

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