Locus specific endogenous retroviral expression associated with Alzheimer's disease

Area of Science:

• Genomics
• Neuroscience
• Molecular Biology

Background:

• Human endogenous retroviruses (HERVs) are ancient retroviral remnants integrated into the human genome.
• Aberrant HERV expression is implicated in various diseases, including neurological disorders.
• The role of HERVs in Alzheimer's disease (AD) pathogenesis remains incompletely understood.

Purpose of the Study:

• To investigate the expression patterns of HERVs in Alzheimer's disease patients.
• To explore the correlation between HERV expression and gene expression in AD.
• To determine the genomic localization of differentially expressed HERVs in relation to disease-associated genes.

Main Methods:

• Combined two public and one novel RNA-Seq datasets from 103 AD patients and 45 healthy controls.
• Utilized the 'telescope' tool for HERV quantification and gene expression analysis.
• Identified differentially expressed genes and HERVs, and analyzed their genomic proximity.

Main Results:

• Identified significant differences in gene and HERV expression between AD patients and controls.
• Discovered numerous differentially expressed HERVs across the genome, with many belonging to the HERV-K superfamily.
• Found correlations between specific HERVs and dysregulated genes involved in AD pathways, often located in close physical proximity.

Conclusions:

• Dysregulated expression of HERVs is a feature of Alzheimer's disease.
• The genomic localization of these HERVs suggests a mechanism by which they may influence pathogenic gene expression in AD.
• These findings highlight HERVs as potential contributors to Alzheimer's disease pathology.