{"doi":"10.1007/s00401-024-02751-9","title":"Brain vasculature accumulates tau and is spatially related to tau tangle pathology in Alzheimer’s disease","abstract":"Insoluble pathogenic proteins accumulate along blood vessels in conditions of cerebral amyloid angiopathy (CAA), exerting a toxic effect on vascular cells and impacting cerebral homeostasis. In this work, we provide new evidence from three-dimensional human brain histology that tau protein, the main component of neurofibrillary tangles, can similarly accumulate along brain vascular segments. We quantitatively assessed n = 6 Alzheimer's disease (AD), and n = 6 normal aging control brains and saw that tau-positive blood vessel segments were present in all AD cases. Tau-positive vessels are enriched for tau at levels higher than the surrounding tissue and appear to affect arterioles across cortical layers (I-V). Further, vessels isolated from these AD tissues were enriched for N-terminal tau and tau phosphorylated at T181 and T217. Importantly, tau-positive vessels are associated with local areas of increased tau neurofibrillary tangles. This suggests that accumulation of tau around blood vessels may reflect a local clearance failure. In sum, these data indicate that tau, like amyloid beta, accumulates along blood vessels and may exert a significant influence on vasculature in the setting of AD.","journal":"Acta Neuropathologica","year":2024,"id":432300,"datarank":0.42498200160843247,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"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":292512,"name":"Nancy E. Ruiz‐Uribe","orcid":"0000-0003-0671-9617","position":1,"is_corresponding":false},{"id":1211185,"name":"Eric del Sastre","orcid":"0000-0003-0772-2279","position":2,"is_corresponding":false},{"id":996035,"name":"Benjamin Woost","orcid":null,"position":3,"is_corresponding":false},{"id":1236886,"name":"Elizabeth Bader","orcid":"0000-0002-1606-0425","position":4,"is_corresponding":false},{"id":1076498,"name":"Joshua Bailey","orcid":null,"position":5,"is_corresponding":false},{"id":19610,"name":"Bradley T. Hyman","orcid":"0000-0002-7959-9401","position":6,"is_corresponding":false},{"id":995725,"name":"Theodore J. Zwang","orcid":"0000-0002-6815-4482","position":7,"is_corresponding":false},{"id":295141,"name":"Rachel E. Bennett","orcid":"0000-0001-9640-0575","position":8,"is_corresponding":false},{"id":1076081,"name":"Zachary Hoglund","orcid":"0009-0008-6490-9957","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:59:35.267142Z","pmid":"38884806","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":[]}