Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease. Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease

We identify and validate 11,039 circular RNAs with high confidence in dopamine and pyramidal neurons --- the preferentially vulnerable prototypical neurons in Parkinson’s and Alzheimer’s --- in 190 human brains using laser-capture RNA sequencing that combines ultra-deep sequencing of polyadenylated and non-polyadenylated RNA with cell-type enrichment afforded by light microscopy. Overall design: To systematically profile the transcriptome of human brain neurons, we have developed the lcRNAseq method to deeply sequence ribo-depleted total RNAs from laser-captured neurons for human post-mortem brains in the BRAINcode project. In brief, dopaminergic neurons (DA) from the midbrain substantia nigra pars compacta of 104 high-quality human brains (DA; HC: n = 59; ILB: n = 27; PD: n = 18), pyramidal neurons from layers V/VI of the middle temporal gyrus of 83 brains (TCPY; HC: n = 40; AD: n = 43) and from the primary motor cortex of three brains (MCPY) were laser-captured. Human fibroblasts from four (FB) and peripheral blood mononuclear white cells from three individuals (PBMC) were analyzed as non-CNS cell types using the same pipeline.