Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.11.088591v1?rss=1 Authors: Otero-Garcia, M., Xue, Y.-Q., Shakouri, T., Deng, Y., Morabito, S., Allison, T., Lowry, W. E., Kawaguchi, R., Swarup, V., Cobos, I. Abstract: Aggregation of hyperphosphorylated tau in neurofibrillary tangles (NFTs) is closely associated with neuronal death and cognitive decline in Alzheimer's disease (AD). To define the signatures that distinguish between aggregation-prone and resistant cell states in AD, we developed a FACS-based method for the high-throughput isolation and transcriptome profiling of individual cells with cytoplasmic aggregates and profiled 63,110 somas from human AD brains. By comparing NFT-bearing and NFT-free somas within and across neuronal subtypes, we identified the cell-type-specific and shared states. NFT-bearing neurons shared a marked upregulation of genes associated with synaptic transmission, including a core set of 63 genes enriched for synaptic vesicle cycle and transsynaptic signaling, whereas glucose metabolism and oxidative phosphorylation changes were highly neuronal-subtype-specific. Apoptosis was modestly enriched in NFT-bearing neurons despite the strong link between tau and cell death. Our datasets provide a resource for investigating tau-mediated neurodegeneration and a platform for biomarker and drug target discovery. Copy rights belong to original authors. Visit the link for more info