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.