{"id":"doi:10.1038/s41591-023-02443-z","kind":"article","title":"CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer's disease","authors":["Horie K","Salvadó G","Barthélemy NR","Janelidze S","Li Y","He Y","Saef B","Chen CD","Jiang H","Strandberg O","Pichet Binette A","Palmqvist S","Sato C","Sachdev P","Koyama A","Gordon BA","Benzinger TLS","Holtzman DM","Morris JC","Mattsson-Carlgren N","Stomrud E","Ossenkoppele R","Schindler SE","Hansson O","Bateman RJ"],"author_count":25,"year":2023,"published":"2023-07-13","venue":"Nature medicine","cited_by":226,"doi":"10.1038/s41591-023-02443-z","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41591-023-02443-z","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41591-023-02443-z","updated":null,"pmid":"37443334","pmcid":"PMC10427417","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC10427417/pdf","abstract":"Aggregated insoluble tau is one of two defining features of Alzheimer's disease. Because clinical symptoms are strongly correlated with tau aggregates, drug development and clinical diagnosis need cost-effective and accessible specific fluid biomarkers of tau aggregates; however, recent studies suggest that the fluid biomarkers currently available cannot specifically track tau aggregates. We show that the microtubule-binding region (MTBR) of tau containing the residue 243 (MTBR-tau243) is a new cerebrospinal fluid (CSF) biomarker specific for insoluble tau aggregates and compared it to multiple other phosphorylated tau measures (p-tau181, p-tau205, p-tau217 and p-tau231) in two independent cohorts (BioFINDER-2, n = 448; and Knight Alzheimer Disease Research Center, n = 219). MTBR-tau243 was most strongly associated with tau-positron emission tomography (PET) and cognition, whereas showing the lowest association with amyloid-PET. In combination with p-tau205, MTBR-tau243 explained most of the total variance in tau-PET burden (0.58 ≤ R 2 ≤ 0.75) and the performance in predicting cognitive measures (0.34 ≤ R 2 ≤ 0.48) approached that of tau-PET (0.44 ≤ R 2 ≤ 0.52). MTBR-tau243 levels longitudinally increased with insoluble tau aggregates, unlike CSF p-tau species. CSF MTBR-tau243 is a specific biomarker of tau aggregate pathology, which may be utilized in interventional trials and in the diagnosis of patients. Based on these findings, we propose to revise the A/T/(N) criteria to include MTBR-tau243 as representing insoluble tau aggregates ('T').","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer's disease\" by Horie K, Salvadó G, Barthélemy NR et al., https://doi.org/10.1038/s41591-023-02443-z, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"neurodegeneration","name":"Alzheimer's, Parkinson's & Neurodegeneration","domain_slug":"medicine"}],"cited_in_dossiers":[]}