{"doi":"10.1101/2020.05.11.088591","title":"Single-soma transcriptomics of tangle-bearing neurons in Alzheimer’s disease reveals the signatures of tau-associated synaptic dysfunction","abstract":"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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":118706,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":46,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":551831,"name":"Yue-Qiang Xue","orcid":"0009-0004-4175-6936","position":1,"is_corresponding":false},{"id":553061,"name":"Tamara Shakouri","orcid":null,"position":2,"is_corresponding":false},{"id":553062,"name":"Yongning Deng","orcid":null,"position":3,"is_corresponding":false},{"id":551832,"name":"Samuel Morabito","orcid":"0000-0002-7768-4856","position":4,"is_corresponding":false},{"id":551833,"name":"Thomas F. Allison","orcid":"0000-0001-5881-6991","position":5,"is_corresponding":false},{"id":461180,"name":"William E. Lowry","orcid":"0000-0003-2932-2276","position":6,"is_corresponding":false},{"id":226817,"name":"Riki Kawaguchi","orcid":"0000-0002-2489-4825","position":7,"is_corresponding":false},{"id":27831,"name":"Vivek Swarup","orcid":"0000-0003-3762-2746","position":8,"is_corresponding":false},{"id":551834,"name":"Inma Cobos","orcid":"0000-0002-2043-1890","position":9,"is_corresponding":false},{"id":551830,"name":"Marcos Otero‐García","orcid":"0000-0002-8830-7001","position":0,"is_corresponding":true}],"reference_count":105,"raw_metadata":null,"created_at":"2026-07-18T23:14:03.409507Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}