Locus specific endogenous retroviral expression associated with Alzheimer’s disease

Published on July 6, 2023

Imagine if our DNA was a crowded city, and scattered throughout were remnants of ancient viruses. These remnants, known as human endogenous retroviruses (HERVs), have long been suspected of playing a role in diseases like Alzheimer’s. To investigate this further, scientists analyzed RNA-Seq datasets from 103 Alzheimer’s patients and 45 healthy individuals. With the help of a tool called telescope, they quantified the expression of HERVs and genes in these samples. The results revealed that certain HERVs were expressed differently in Alzheimer’s patients, and their locations in the genome hinted at how they may influence disease pathways. By examining the correlation between HERVs and dysregulated genes, the researchers gained insight into how these elements contribute to the development of Alzheimer’s. This study opens up new avenues for understanding the intricate mechanisms underlying this devastating disease!

IntroductionHuman endogenous retroviruses (HERVs) are transcriptionally-active remnants of ancient retroviral infections that may play a role in Alzheimer’s disease.MethodsWe 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.ResultsWe 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 Alzheimer’s and are physically proximal to genes which drive disease pathways.DiscussionDysregulated 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.

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