{"doi":"10.1002/dad2.70227","title":"Diagnostic utility of plasma p‐tau217 differs by Alzheimer's disease tau‐based subtypes","abstract":"Introduction: Blood-based biomarkers, most notably plasma phosphorylated tau (p-tau)217, have transformed the diagnostic landscape of Alzheimer's disease (AD). Methods: We applied an unsupervised machine learning approach to tau positron emission tomography (PET) imaging in 606 participants (age 73.95 ± 7.72; 309 female) to identify AD subtypes. Within each subtype, we evaluated plasma p-tau217 levels, their association with regional tau PET uptake, differences between cognitively unimpaired (CU) and cognitively impaired (CI) individuals, and relationships to cognitive performance. Results: Four subtypes were identified: limbic, medial temporal lobe (MTL) sparing, posterior, and lateral temporal (l temporal). Plasma p-tau217 was elevated in CI versus CU in limbic, posterior, and l temporal subtypes and strongly associated with tau deposition and cognitive performance. In the MTL-sparing subtype, p-tau217 showed a significant association with tau but no elevation in CI and no relationship to cognition. Discussion: These findings indicate that p-tau217's diagnostic utility varies across AD subtypes, reflecting distinct biological mechanisms not captured by current blood biomarkers. Highlights: Plasma phosphorylated tau (p-tau)217 differentiated cognitively unimpaired from impaired individuals in most subtypes, with the notable limitation of the medial temporal lobe (MTL)-sparing group.P-tau217 level was linked to regional tau accumulation as measured by tau positron emission tomography, across all subtypes.The MTL-sparing subtype appeared to be unique, as p-tau217 was not elevated in cognitively impaired individuals, and there was no clear relationship between p-tau217 levels and cognitive performance.","journal":"Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring","year":2025,"id":548950,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"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":746902,"name":"Tracy Butler","orcid":"0000-0003-0130-8122","position":1,"is_corresponding":false},{"id":1443096,"name":"Shahram Zare","orcid":null,"position":2,"is_corresponding":false},{"id":1442623,"name":"Ali Reihanian","orcid":"0000-0001-6668-3535","position":3,"is_corresponding":false},{"id":1442624,"name":"Mohammad Khalafi","orcid":"0000-0002-9447-5167","position":4,"is_corresponding":false},{"id":282465,"name":"Nancy S. Foldi","orcid":"0000-0001-8810-8558","position":5,"is_corresponding":false},{"id":899468,"name":"Sudhin A. Shah","orcid":"0000-0003-4116-1989","position":6,"is_corresponding":false},{"id":1443097,"name":"Hasan Jafari","orcid":null,"position":7,"is_corresponding":false},{"id":263826,"name":"Yi Li","orcid":"0000-0002-3875-3513","position":8,"is_corresponding":false},{"id":725495,"name":"Liangdong Zhou","orcid":"0000-0002-8389-274X","position":9,"is_corresponding":false},{"id":1204659,"name":"William Jones Dartora","orcid":"0000-0002-6164-0031","position":10,"is_corresponding":false},{"id":1294971,"name":"Krista Minéia Wartchow","orcid":"0000-0003-4572-3600","position":11,"is_corresponding":false},{"id":632903,"name":"Laura Beth McIntire","orcid":"0000-0002-9565-8889","position":12,"is_corresponding":false},{"id":917565,"name":"Gloria Chiang","orcid":"0000-0001-9925-0816","position":13,"is_corresponding":false},{"id":300139,"name":"for the Alzheimer's Disease Neuroimaging Initiative","orcid":null,"position":14,"is_corresponding":false},{"id":812622,"name":"Seyed Hani Hojjati","orcid":"0000-0003-3900-9603","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T02:54:03.053965Z","pmid":"41322377","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":[]}