Single nuclear RNA sequencing reveals pathways related to neuronal vulnerability in Alzheimers disease

Neuronal loss is the ultimate driver of neural system dysfunction in Alzheimers Disease (AD). We used single nuclear RNAseq and neuropathological phenotyping to elucidate mechanisms of neurodegeneration in AD by identifying vulnerable neuronal populations and probing for their differentially expressed genes. Evidenced by transcriptomic analyses and quantitative tau immunoassays of human control and AD brain tissue, we identify a neuronal population especially vulnerable to tau pathology. Multiplexed immunohistochemistry and in situ hybridization (CBLN2 and LINC00507) validate the presence of the tau-vulnerable neuronal population and reveal a propensity of this population to bear tau pathology.