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

• Published in: Neuron (Cambridge, Mass.) Mass.), 2020-03, Vol.105 (6), p.1027-1035.e2
• Main Authors: Allnutt, Mary Alice, Johnson, Kory, Bennett, David A., Connor, Sarah M., Troncoso, Juan C., Pletnikova, Olga, Albert, Marilyn S., Resnick, Susan M., Scholz, Sonja W., De Jager, Philip L., Jacobson, Steven
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - virology; Alzheimer's disease; Brain; Brain - virology; Case-Control Studies; Cohort Studies; Cytomegalovirus; Datasets; Dementia; Deoxyribonucleic acid; Disease; DNA; DNA sequencing; DNA viruses; Encephalitis; Epstein-Barr virus; Female; Genetic testing; Herpes viruses; herpesvirus; Herpesvirus 6, Human - genetics; Herpesvirus 6, Human - isolation & purification; human herpesvirus 6; Humans; Infections; Male; Multiple sclerosis; Neurodegenerative diseases; Pathogenesis; Pathogens; Ribonucleic acid; RNA; Sequence Analysis, DNA - statistics & numerical data; Sequence Analysis, RNA - statistics & numerical data; Viral infections
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2019.12.031

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. •RNA-seq data from two Alzheimer’s disease (AD) cohorts were screened for 118 viruses•DNA from 711 AD and control brains was analyzed for PCR reactivity to HHV-6A and/or HHV-6B•HHV-6 demonstrated little specificity to AD brains over controls by either method•These complementary methods do not support strong association between HHV-6 and AD Allnutt et al. screen three independent Alzheimer’s disease (AD) cohorts for pathogens, including 118 human viruses, using RNA-seq and PCR from 711 AD and non-AD control brains. No differences in viral detection between AD and non-AD controls are observed.