{"doi":"10.1016/j.celrep.2024.114574","title":"Neurofibrillary tangle-bearing neurons have reduced risk of cell death in mice with Alzheimer’s pathology","abstract":"A prevailing hypothesis is that neurofibrillary tangles play a causal role in driving cognitive decline in Alzheimer's disease (AD) because tangles correlate anatomically with areas that undergo neuronal loss. We used two-photon longitudinal imaging to directly test this hypothesis and observed the fate of individual neurons in two mouse models. At any time point, neurons without tangles died at >3 times the rate as neurons with tangles. Additionally, prior to dying, they became >20% more distant from neighboring neurons across imaging sessions. Similar microstructural changes were evident in a population of non-tangle-bearing neurons in Alzheimer's donor tissues. Together, these data suggest that nonfibrillar tau puts neurons at high risk of death, and surprisingly, the presence of a tangle reduces this risk. Moreover, cortical microstructure changes appear to be a better predictor of imminent cell death than tangle status is and a promising tool for identifying dying neurons in Alzheimer's.","journal":"Cell Reports","year":2024,"id":420293,"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":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1211185,"name":"Eric del Sastre","orcid":"0000-0003-0772-2279","position":1,"is_corresponding":false},{"id":1211691,"name":"Nina Wolf","orcid":null,"position":2,"is_corresponding":false},{"id":292512,"name":"Nancy E. Ruiz‐Uribe","orcid":"0000-0003-0671-9617","position":3,"is_corresponding":false},{"id":996035,"name":"Benjamin Woost","orcid":null,"position":4,"is_corresponding":false},{"id":1076081,"name":"Zachary Hoglund","orcid":"0009-0008-6490-9957","position":5,"is_corresponding":false},{"id":229909,"name":"Zhanyun Fan","orcid":null,"position":6,"is_corresponding":false},{"id":1076498,"name":"Joshua Bailey","orcid":null,"position":7,"is_corresponding":false},{"id":1211692,"name":"Lois Nfor","orcid":null,"position":8,"is_corresponding":false},{"id":336996,"name":"Luc Buée","orcid":"0000-0002-6261-4230","position":9,"is_corresponding":false},{"id":335165,"name":"K. Peter R. Nilsson","orcid":"0000-0002-5582-140X","position":10,"is_corresponding":false},{"id":19610,"name":"Bradley T. Hyman","orcid":"0000-0002-7959-9401","position":11,"is_corresponding":false},{"id":295141,"name":"Rachel E. Bennett","orcid":"0000-0001-9640-0575","position":12,"is_corresponding":false},{"id":995725,"name":"Theodore J. Zwang","orcid":"0000-0002-6815-4482","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T01:57:25.777459Z","pmid":"39096489","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":[]}