{"doi":"10.1111/jnc.70114","title":"Equivalence of Plasma and Serum for Clinical Measurement of p‐tau217: Comparative Analyses of Four Blood‐Based Assays","abstract":"Phosphorylated tau (p-tau) 217 is a promising blood biomarker for Alzheimer's disease (AD). However, most p-tau217 assays have been validated solely in ethylenediaminetetraacetic acid (EDTA) plasma, leaving the clinical applicability of serum p-tau217 largely unexplored despite serum being a preferred matrix in many clinical laboratories. To address this gap, we compared p-tau217 concentrations and classification accuracies in matched plasma and serum samples in four research-use-only assays. Paired plasma and serum samples were processed from the same venipuncture collection and assessed with each of the four p-tau217 assays following manufacturer-recommended procedures in two research cohorts from the University of Pittsburgh Azheimer's Disease Research Center (Pitt-ADRC; n = 50) and the Human Connectome Project (n = 34). The four assays evaluated included three from commercial sources-Lumipulse (recently gained FDA approval), ALZpath, and NULISA-and another from the University of Pittsburgh (Pittsburgh plasma p-tau217). Plasma and serum p-tau217 levels varied across assays; the ALZpath, Pittsburgh, and NULISA methods showed significantly lower p-tau217 levels in serum compared with plasma (p < 0.0001) for both cohorts, while Lumipulse showed higher plasma levels in the Pitt-ADRC cohort but equivalent plasma and serum levels in the HCP cohort. Yet, strong correlations (rho > 0.8) were observed between plasma and serum p-tau217 pairs for all methods. Both plasma and serum p-tau217 demonstrated strong classification accuracies to differentiate clinical AD from normal controls, with high AUC (up to 0.963) for all methods. The exception was the Pittsburgh assay, where plasma p-tau217 had significantly superior AUC to serum p-tau217 (plasma: 0.912, serum: 0.844). The rest of the assays had equivalent accuracies in both matrices. Serum p-tau217 performs equivalently as plasma p-tau217 for most assessed assays. Serum can be used as a substitute for plasma in the use of most p-tau217 assays to evaluate Aβ pathology in AD for both research and clinical purposes.","journal":"Journal of Neurochemistry","year":2025,"id":512600,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"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":1372722,"name":"Ally L. Albert","orcid":null,"position":1,"is_corresponding":false},{"id":425004,"name":"Anuradha Sehrawat","orcid":"0000-0002-7243-5447","position":2,"is_corresponding":false},{"id":1372723,"name":"M. Carmen Fariñas","orcid":null,"position":3,"is_corresponding":false},{"id":1070646,"name":"Óscar López","orcid":"0000-0003-2896-6993","position":4,"is_corresponding":false},{"id":518875,"name":"Xuemei Zeng","orcid":"0000-0003-4885-4788","position":5,"is_corresponding":false},{"id":329924,"name":"Ann D. Cohen","orcid":"0000-0001-7395-9624","position":6,"is_corresponding":false},{"id":241105,"name":"Thomas K. Karikari","orcid":"0000-0003-1422-4358","position":7,"is_corresponding":false},{"id":1245147,"name":"Yijun Chen","orcid":"0009-0001-4579-4057","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T02:48:06.263458Z","pmid":"40600294","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":[]}