Alternative splicing is an important post-transcriptional regulatory mechanism through which pre-mRNA molecules can produce multiple distinct mRNAs. Alternative splicing affects over 95% of human genes1, contributing significantly to the functional diversity and complexity of proteins expressed in tissues2. Alternative splicing is abundant in human nervous system tissues3 and contributes to phenotypic differences within and between individuals: at least 20% of disease-causing mutations may affect pre-mRNA splicing4. Mutations in RNA-binding proteins (RBPs) involved in splicing regulation and aberrant splicing have been linked to Amyotrophic lateral sclerosis (ALS)5 and Autism6. Further, disruptions in RNA metabolism, including mRNA splicing, are associated with age-related disorders, such as Frontotemporal lobar dementia (FTD)7, Parkinson’s disease8 and Alzheimer’s disease9,10. These studies have largely focused on alternative splicing of selected candidate genes, including the amyloid precursor protein (APP) 8 and microtubule associated protein Tau (MAPT)8,9,11. However, proteomic profiles of Alzheimer’s disease brains identified an increased aggregation of insoluble U1 snRNP, a small nuclear RNA (snRNA) component of the spliceosomal complex, suggesting that the core splicing machinery may be altered in Alzheimer’s disease12. Apart from these studies, there have
