In Silico Screening of Long-Read Sequencing Data for Endogenous Viral Elements in Alzheimer’s Disease Patients And Centenarians
E.E.W. Ma (TU Delft - Electrical Engineering, Mathematics and Computer Science)
M.J.T. Reinders – Mentor (TU Delft - Pattern Recognition and Bioinformatics)
N. Tesi – Graduation committee member (TU Delft - Pattern Recognition and Bioinformatics)
Christoph Lofi – Graduation committee member (TU Delft - Web Information Systems)
More Info
expand_more
Other than for strictly personal use, it is not permitted to download, forward or distribute the text or part of it, without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license such as Creative Commons.
Abstract
Ever since the origin of human life, we have been infected by a wide range of viruses. These pathogens have invaded our cells, leaving behind traces of their presence in our genome, known as endogenous viral elements (EVEs). Among the affected cells are neurons. The infectious hypothesis for Alzheimer's disease (AD) proposes that viral infections may serve as an environmental factor contributing to AD. In our study, we explored this hypothesis for the first time from an endogenous perspective by identifying EVEs in the genomes of both AD patients and cognitively healthy centenarians (CHCs). Using a custom-built data processing pipeline, our findings reveal that the genomes of AD patients on average harbor more EVEs than those of CHCs (p=3.24e-4, incidence rate ratio (IRR) = 1.27). Furthermore, we identified specific chromosomal regions with a higher incidence of viral integration in the AD cohort across different virus families. Our data suggest that viral infections over time have increased the susceptibility to AD, underscoring the importance of preventive measures against infections.