{"doi":"10.1093/brain/awae346","title":"A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests","abstract":"Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarker for reliable detection of Alzheimer's disease pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET and cognition as outcomes and benchmarked them against CSF biomarker tests. Samples from 998 individuals [mean (range) age 68.5 (20.0-92.5) years, 53% female] from the Swedish BioFINDER-2 cohort, including both cognitively unimpaired and cognitively impaired individuals, were analysed. Plasma p-tau217 was measured with mass spectrometry assays [the ratio between phosphorylated and non-phosphorylated (%p-tau217WashU) and p-tau217WashU] and with immunoassays (p-tau217Lilly, p-tau217Janssen and p-tau217ALZpath). CSF biomarkers included p-tau217Lilly, the US Food and Drug Administration-approved p-tau181/Aβ42Elecsys, and p-tau181Elecsys. All plasma p-tau217 tests exhibited a high ability to detect abnormal Aβ-PET [area under the curve (AUC) range: 0.91-0.96] and tau-PET (AUC range: 0.94-0.97). Plasma %p-tau217WashU had the highest performance, with significantly higher AUCs than all the immunoassays (Pdiff < 0.007). For detecting Aβ-PET status, %p-tau217WashU had an accuracy of 0.93 (immunoassays: 0.83-0.88), sensitivity of 0.91 (immunoassays: 0.84-0.87) and a specificity of 0.94 (immunoassays: 0.85-0.89). Among immunoassays, p-tau217Lilly and plasma p-tau217ALZpath had higher AUCs than plasma p-tau217Janssen for Aβ-PET status (Pdiff < 0.006), and p-tau217Lilly outperformed plasma p-tau217ALZpath for tau-PET status (Pdiff = 0.025). Plasma %p-tau217WashU exhibited stronger associations with all PET load outcomes compared with immunoassays; baseline Aβ-PET load (R2: 0.72; immunoassays: 0.47-0.58; Pdiff < 0.001), baseline tau-PET load (R2: 0.51; immunoassays: 0.38-0.45; Pdiff < 0.001), longitudinal Aβ-PET load (R2: 0.53; immunoassays: 0.31-0.38; Pdiff < 0.001) and longitudinal tau-PET load (R2: 0.50; immunoassays: 0.35-0.43; Pdiff < 0.014). Among immunoassays, plasma p-tau217Lilly was more associated with Aβ-PET load than plasma p-tau217Janssen (Pdiff < 0.020) and with tau-PET load than both plasma p-tau217Janssen and plasma p-tau217ALZpath (all Pdiff < 0.010). Plasma %p-tau217 also correlated more strongly with baseline cognition (Mini-Mental State Examination) than all immunoassays (R2: %p-tau217WashU: 0.33; immunoassays: 0.27-0.30; Pdiff < 0.024). The main results were replicated in an external cohort from Washington University in St Louis (n = 219). Finally, p-tau217NULISA showed similar performance to other immunoassays in subsets of both cohorts. In summary, both mass spectrometry- and immunoassay-based p-tau217 tests generally perform well in identifying Aβ-PET, tau-PET and cognitive abnormalities, but %p-tau217WashU performed significantly better than all the examined immunoassays. Plasma %p-tau217 may be considered as a stand-alone confirmatory test for Alzheimer's disease pathology, whereas some immunoassays might be better suited as triage tests where positive results are confirmed with a second test, which needs to be determined by future reviews incorporating results from multiple cohorts.","journal":"Brain","year":2024,"id":416761,"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":102,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9463,"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":658019,"name":"Gemma Salvadó","orcid":"0000-0002-5210-9230","position":1,"is_corresponding":false},{"id":230943,"name":"Shorena Janelidze","orcid":"0000-0003-2869-8378","position":2,"is_corresponding":false},{"id":230942,"name":"Niklas Mattsson","orcid":"0000-0002-8885-7724","position":3,"is_corresponding":false},{"id":1201342,"name":"Divya Bali","orcid":"0000-0003-3178-1586","position":4,"is_corresponding":false},{"id":1201343,"name":"Anna Orduña Dolado","orcid":"0009-0003-8287-0754","position":5,"is_corresponding":false},{"id":74385,"name":"Hartmuth C. Kolb","orcid":"0000-0003-2414-5792","position":6,"is_corresponding":false},{"id":353468,"name":"Gallen Triana‐Baltzer","orcid":"0000-0003-0612-1236","position":7,"is_corresponding":false},{"id":228356,"name":"Nicolas R. Barthélemy","orcid":"0000-0003-4937-2860","position":8,"is_corresponding":false},{"id":310970,"name":"Suzanne E. Schindler","orcid":"0000-0002-1680-1465","position":9,"is_corresponding":false},{"id":479431,"name":"Andrew J. Aschenbrenner","orcid":"0000-0002-4317-7282","position":10,"is_corresponding":false},{"id":67984,"name":"Cyrus A. Raji","orcid":"0000-0002-9086-0105","position":11,"is_corresponding":false},{"id":301875,"name":"Tammie L.S. Benzinger","orcid":"0000-0002-8114-0552","position":12,"is_corresponding":false},{"id":245388,"name":"Peter R. Schofield","orcid":"0000-0003-2967-9662","position":13,"is_corresponding":false},{"id":17647,"name":"Laura Ibáñez","orcid":"0000-0003-2381-7059","position":14,"is_corresponding":false},{"id":17614,"name":"Jigyasha Timsina","orcid":"0000-0003-4794-9187","position":15,"is_corresponding":false},{"id":867455,"name":"Carlos Cruchaga","orcid":"0000-0002-5261-689X","position":16,"is_corresponding":false},{"id":228359,"name":"Randall J. Bateman","orcid":"0000-0002-7729-1702","position":17,"is_corresponding":false},{"id":241104,"name":"Nicholas J. Ashton","orcid":"0000-0002-3579-8804","position":18,"is_corresponding":false},{"id":1038452,"name":"Burak Arslan","orcid":"0000-0001-7229-3226","position":19,"is_corresponding":false},{"id":27601,"name":"Henrik Zetterberg","orcid":"0000-0003-3930-4354","position":20,"is_corresponding":false},{"id":27600,"name":"Kaj Blennow","orcid":"0000-0002-1890-4193","position":21,"is_corresponding":false},{"id":561487,"name":"Alexa Pichet Binette","orcid":"0000-0001-5218-3337","position":22,"is_corresponding":false},{"id":65584,"name":"Oskar Hansson","orcid":"0000-0001-8467-7286","position":23,"is_corresponding":false},{"id":1201995,"name":"Noëlle Warmenhoven","orcid":null,"position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T01:56:44.873714Z","pmid":"39468767","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":[]}