Reanalysis of Alzheimer’s Brain Sequencing Data Reveals Absence of Purported HHV6A and HHV7

Abstract

Readhead et al. recently reported in Neuron the detection and association of Human Herpesviruses 6A (HHV6A) and 7 (HHV7) with Alzheimer's disease by shotgun sequencing. I was skeptical of the specificity of their modified Viromescan bioinformatics method and subsequent analysis for numerous reasons. In their supplementary data, they report the detection of Variola virus, the etiological agent of the eradicated disease smallpox, in 97.5% of their Mount Sinai Brain Bank dataset. I reanlyzed Readhead et al's data using highly sensitive and specific alternative methods and find no HHV7 reads in their samples; HHV6A reads were found in only 2 out of their top 15 samples sorted by reported HHV6A abundance. Finally, I recreate Readhead et al's modified Viromescan method and identify reasons for its low specificity.