Biology of splicing in Alzheimer's disease research

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease, leading to dementia in the aging human brain. Although a huge amount of research has been done to date, the pathogenesis of AD remains largely unknown. Given the dominance of mRNA splicing in the nervous system, it would be invaluable to precisely identify mis-splicing in the AD brain to understand more deeply how the gene network orchestrates the development of pathology in affected cells. In this brief manuscript, we first introduce the term mRNA splicing and discuss its abnormality in the AD brain. Then, we describe the technical challenges of the precise detection of mis-splicing, as well as their reasonable solutions. Finally, we discuss the future directions for splicing biology in AD.

Keywords: Alternative splicing; Alzheimer's disease; Brain heterogeneity; Long-read sequencing; Short-read sequencing; Single-cell transcriptome analysis.