Splicing transcriptome analysis reveals retained introns in retinal genes of the 5xFAD mouse, suggesting early diagnosis of Alzheimer’s disease through vision impairment

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which neuronal and synaptic loss of the brain leads to cognitive impairment and dementia. Therefore, the early diagnosis of AD with various biomarkers is important for the prevention and treatment. Although retina pathology is emerging biomarker that associated with AD, detailed molecular mechanisms of retinal impairments remain unclear. Here, we identify the genome-wide dysfunction of alternative splicing in the early stage of 5xFAD transgenic mouse retina by the RNA-seq analysis. Especially, retained intron (RI) highly enriched in phototransduction and retinal genes of 1.5-month-old 5xFAD mouse retina that significantly associated with retinal physiological impairment of rod photoreceptors by electroretinogram (ERG) analysis. These results indicate that the abnormal scotopic ERG associated with global splicing impairment may be useful early detection biomarker for AD. We compared transcript and retained intron expression profiles between mouse retina of wild type and 5xFAD. RNA-seq for 1-month and 6-month were performed in mouse retina between wild type and 5xFAD.