@article{5997329defac49f0be50e2fe185af2a4,
title = "Human Herpesvirus 6 Detection in Alzheimer's Disease Cases and Controls across Multiple Cohorts",
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",
author = "Allnutt, {Mary Alice} and Kory Johnson and Bennett, {David A.} and Connor, {Sarah M.} and Troncoso, {Juan C.} and Olga Pletnikova and Albert, {Marilyn S.} and Resnick, {Susan M.} and Scholz, {Sonja W.} and {De Jager}, {Philip L.} and Steven Jacobson",
note = "Funding Information: This work was supported by the Intramural Research Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health . Funding Information: DNA samples from ROSMAP were provided by the Rush Alzheimer{\textquoteright}s Disease Center and can be requested along with data from https://www.radc.rush.edu . DNA from the JHBRC cohort was provided by Dr. Sonja Scholz in collaboration with the Johns Hopkins Department of Neurology. This research was supported in part by the Intramural Research Program of the NIH National Institute of Neurological Disorders and Stroke (project number: ZIA-NS003154). We would like to thank the NIA Baltimore Longitudinal Study of Aging for contributing tissue samples to the Johns Hopkins Alzheimer{\textquoteright}s Disease Research Center. The results published here are in whole or in part based on data obtained from the AMP-AD Knowledge Portal ( https://doi.org/10.7303/syn2580853 ; https://doi.org/10.1038/s41593-018-0154-9 ). Study data were provided by the Rush Alzheimer{\textquoteright}s Disease Center, Rush University Medical Center, Chicago. Data collection was supported through funding by NIA grants P30AG10161 , R01AG15819 , R01AG17917 , R01AG30146 , R01AG36836 , U01AG32984 , U01AG46152 , and U01AG61356 , in addition to JHU ADRC ( P50AG05146 ), the Illinois Department of Public Health , the Translational Genomics Research Institute , and the Intramural Research Program of the National Institute on Aging, NIH . These data were generated from postmortem brain tissue collected through the Mount Sinai VA Medical Center Brain Bank and were provided by Dr. Eric Schadt from Mount Sinai School of Medicine. Funding Information: This work was supported by the Intramural Research Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health. DNA samples from ROSMAP were provided by the Rush Alzheimer's Disease Center and can be requested along with data from https://www.radc.rush.edu. DNA from the JHBRC cohort was provided by Dr. Sonja Scholz in collaboration with the Johns Hopkins Department of Neurology. This research was supported in part by the Intramural Research Program of the NIH National Institute of Neurological Disorders and Stroke (project number: ZIA-NS003154). We would like to thank the NIA Baltimore Longitudinal Study of Aging for contributing tissue samples to the Johns Hopkins Alzheimer's Disease Research Center. The results published here are in whole or in part based on data obtained from the AMP-AD Knowledge Portal (https://doi.org/10.7303/syn2580853; https://doi.org/10.1038/s41593-018-0154-9). Study data were provided by the Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago. Data collection was supported through funding by NIA grants P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36836, U01AG32984, U01AG46152, and U01AG61356, in addition to JHU ADRC (P50AG05146), the Illinois Department of Public Health, the Translational Genomics Research Institute, and the Intramural Research Program of the National Institute on Aging, NIH. These data were generated from postmortem brain tissue collected through the Mount Sinai VA Medical Center Brain Bank and were provided by Dr. Eric Schadt from Mount Sinai School of Medicine. M.A.A. S.J. and K.J. contributed to the study's overall conception, design, and interpretation. M.A.A. and S.J. wrote the manuscript, while M.A.A. and K.J. created the figures with input from S.J. K.J. conducted analysis of RNA-seq data, while M.A.A. conducted PCR analysis of all DNA samples. S.W.S. provided DNA samples from JHBRC, and P.L.D. provided DNA samples from ROSMAP. S.M.C. performed quantification and preparation of DNA samples from ROSMAP. D.A.B. is the principal investigator behind ROSMAP. J.C.T. and O.P. are the neuropathologists from the Hopkins Brain Resource Center who performed the pathological evaluation of the included samples from JHBRC; M.S.A. and S.M.R. recruited many of the AD cases and controls that are in the JHBRC. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019",
year = "2020",
month = mar,
day = "18",
doi = "10.1016/j.neuron.2019.12.031",
language = "English (US)",
volume = "105",
pages = "1027--1035.e2",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",
}