{"doi":"10.1002/alz.14550","title":"Plasma N‐terminal tau fragment is an amyloid‐dependent biomarker in Alzheimer's disease","abstract":"INTRODUCTION: Novel fluid biomarkers for tracking neurodegeneration specific to Alzheimer's disease (AD) are greatly needed. METHODS: Using two independent well-characterized cohorts (n = 881 in total), we investigated the group differences in plasma N-terminal tau (NT1-tau) fragments across different AD stages and their association with cross-sectional and longitudinal amyloid beta (Aβ) plaques, tau tangles, brain atrophy, and cognitive decline. RESULTS: Plasma NT1-tau significantly increased in symptomatic AD and displayed positive associations with Aβ PET (positron emission tomography) and tau PET. Higher baseline NT1-tau levels predicted greater tau PET, with 2- to 10-year intervals and faster longitudinal Aβ PET increases, AD-typical neurodegeneration, and cognitive decline. Plasma NT1-tau showed negative correlations with baseline regional brain volume and thickness, superior to plasma brain-derived tau (BD-tau) and neurofilament light (NfL) in Aβ-positive participants. DISCUSSION: This study suggests that plasma NT1-tau is an Aβ-dependent biomarker and outperforms BD-tau and NfL in detecting cross-sectional neurodegeneration in the AD continuum. HIGHLIGHTS: Plasma N-terminal tau (NT1-tau) was specifically increased in the A+/T+ stage. Plasma NT1-tau was positively associated with greater amyloid beta (Aβ) and tau PET (positron emission tomography) accumulations. Higher plasma NT1-tau predicted greater tau burden and faster Aβ increases. Plasma NT1-tau was more related to neurodegeneration than plasma brain-derived tau (BD-tau) and neurofilament light (NfL).","journal":"Alzheimer s & Dementia","year":2025,"id":516904,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1377532,"name":"Laihong Zhang","orcid":null,"position":1,"is_corresponding":false},{"id":708819,"name":"Anqi Li","orcid":"0000-0001-7919-5784","position":2,"is_corresponding":false},{"id":1332488,"name":"Wenqing Ran","orcid":null,"position":3,"is_corresponding":false},{"id":1383263,"name":"Jieqin Lv","orcid":null,"position":4,"is_corresponding":false},{"id":839573,"name":"Fernando González‐Ortiz","orcid":"0000-0001-7897-9456","position":5,"is_corresponding":false},{"id":881829,"name":"Yue Cai","orcid":"0000-0002-3711-5325","position":6,"is_corresponding":false},{"id":1235234,"name":"Pan Sun","orcid":"0000-0002-7135-2631","position":7,"is_corresponding":false},{"id":1038228,"name":"Lin Liu","orcid":"0000-0001-9672-0042","position":8,"is_corresponding":false},{"id":1235233,"name":"Jie Yang","orcid":"0000-0002-6369-4447","position":9,"is_corresponding":false},{"id":1383264,"name":"Zhengbo He","orcid":null,"position":10,"is_corresponding":false},{"id":1054833,"name":"Lili Fang","orcid":"0000-0002-9834-8069","position":11,"is_corresponding":false},{"id":15052,"name":"Xin Zhou","orcid":"0000-0002-1407-7952","position":12,"is_corresponding":false},{"id":1006366,"name":"Yalin Zhu","orcid":null,"position":13,"is_corresponding":false},{"id":693576,"name":"Zhen Liu","orcid":"0000-0002-5978-3412","position":14,"is_corresponding":false},{"id":1235232,"name":"Xuhui Chen","orcid":"0000-0002-9791-2051","position":15,"is_corresponding":false},{"id":1062959,"name":"Xiang Fan","orcid":"0000-0002-1685-8373","position":16,"is_corresponding":false},{"id":889959,"name":"Dai Shi","orcid":null,"position":17,"is_corresponding":false},{"id":1090187,"name":"Chenghui Ye","orcid":null,"position":18,"is_corresponding":false},{"id":1006367,"name":"Linsen Xu","orcid":null,"position":19,"is_corresponding":false},{"id":917198,"name":"Qingyong Wang","orcid":"0000-0003-2376-5105","position":20,"is_corresponding":false},{"id":27600,"name":"Kaj Blennow","orcid":"0000-0002-1890-4193","position":21,"is_corresponding":false},{"id":881992,"name":"Guanxun Cheng","orcid":"0000-0001-9168-1670","position":22,"is_corresponding":false},{"id":300139,"name":"for the Alzheimer's Disease Neuroimaging Initiative","orcid":null,"position":23,"is_corresponding":false},{"id":1383265,"name":"Pengcheng Ran","orcid":null,"position":24,"is_corresponding":false},{"id":1382802,"name":"Lu Wang","orcid":"0000-0002-4165-4022","position":25,"is_corresponding":false},{"id":277015,"name":"Tengfei Guo","orcid":"0000-0003-2982-0865","position":26,"is_corresponding":false},{"id":881828,"name":"Guoyu Lan","orcid":"0000-0003-2925-1738","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:48:54.768083Z","pmid":"39821479","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":[]}