AUTHOR=Dawson Tyson , Rentia Uzma , Sanford Jessie , Cruchaga Carlos , Kauwe John S. K. , Crandall Keith A. 

TITLE=Locus specific endogenous retroviral expression associated with Alzheimer’s disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 15 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1186470

DOI=10.3389/fnagi.2023.1186470

ISSN=1663-4365

ABSTRACT=INTRODUCTION: Human endogenous retroviruses (HERVs) are transcriptionally-active remnants of ancient retroviral infections that may play a role in Alzheimer's disease.METHODS: We combined two, publicly available RNA-Seq datasets with a third, novel dataset for a total cohort of 103 patients with Alzheimer's disease and 45 healthy controls. We use Telescope to perform HERV quantification for these samples and simultaneously perform gene expression analysis. 2 RESULTS: We identify differentially expressed genes and differentially expressed HERVs in Alzheimer's disease patients. Differentially expressed HERVs are scattered throughout the genome; many of them are members of the HERV-K superfamily. A number of HERVs are correlated with the expression of dysregulated genes in Alzheimers and are physically proximal to genes which drive disease pathways. DISCUSSION: Dysregulated expression of ancient retroviral insertions in the human genome are present in Alzheimer's disease and show localization patterns that may explain how these elements drive pathogenic gene expression.