London Calling 2023: Exploring the impact of mobile elements on Alzheimer's disease using targeted long-read sequencing

Alzheimer's disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of beta-amyloid and tau proteins. While genetic risk factors, such as the APOE e4 variant, have been identified, the genetic basis of AD is not yet fully understood. Recent research suggests that transposable element expression may play a role in neuroinflammation and AD. Transposable elements are an important source of variation within the population, and mobile element insertions (MEIs) can influence genome structure and gene expression; however, mapping MEIs can be challenging due to their repetitive nature. Long-read sequencing has enabled advances in characterizing MEIs. Here, we use nanopore Cas9- targeted sequencing (nCATS) to capture L1HS, AluYa5, and AluYb8 insertions in post-mortem brains of individuals with and without AD. We are able to obtain high coverage over target elements and compare MEIs between patient groups and brain regions.