{"doi":"10.1002/alz.14619","title":"Blood biomarkers differentiate AD‐related versus non‐AD‐related cognitive deficits","abstract":"INTRODUCTION: The utility of blood-based biomarkers for discriminating Alzheimer's disease (AD)-related versus non-AD-related cognitive deficits in preclinical populations remains poorly understood. Here, we tested the capability of blood markers to detect and discriminate variation in performance across multiple cognitive domains in a cognitively unimpaired sample. METHODS: Participants (n = 648, aged 69.9 ± 3.8, 71% female) underwent a comprehensive cognitive assessment and assays for plasma-based biomarkers amyloid beta (Aβ)1-42/1-40 by mass spectrometry, phosphorylated tau (p-tau) 181 and 217, p-tau217/Aβ1-42, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). RESULTS: Greater p-tau217 was exclusively associated with poorer episodic memory performance (β = -0.11, SE = 0.04, p = .003), and remained so after covarying for NfL. Higher NfL was non-specifically associated with poorer performance across a range of cognitive domains and remained so after covarying for p-tau217. DISCUSSION: Blood-based biomarkers may differentiate non-AD-related versus AD-related cognitive deficits. This characterization will be important for early intervention and disease monitoring for AD. HIGHLIGHTS: There is heterogeneity in the causes of cognitive decline in aging. AD-related blood biomarkers may help characterize these causes. Elevated p-tau217 was exclusively associated with poorer episodic memory. Elevated NfL was associated with poorer cognition in a broad range of domains. Blood biomarkers may help differentiate AD- and non-AD-related cognitive deficits.","journal":"Alzheimer s & Dementia","year":2025,"id":510774,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7959,"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":678219,"name":"Lauren E. Oberlin","orcid":"0000-0001-9553-8070","position":1,"is_corresponding":false},{"id":241105,"name":"Thomas K. Karikari","orcid":"0000-0003-1422-4358","position":2,"is_corresponding":false},{"id":1121387,"name":"Marcos Olvera‐Rojas","orcid":"0000-0001-7922-1647","position":3,"is_corresponding":false},{"id":1134162,"name":"Lu Wan","orcid":"0000-0001-8939-3004","position":4,"is_corresponding":false},{"id":583154,"name":"Jill K. Morris","orcid":"0000-0001-5911-4190","position":5,"is_corresponding":false},{"id":760762,"name":"Paul J. Kueck","orcid":"0000-0002-9102-2058","position":6,"is_corresponding":false},{"id":518875,"name":"Xuemei Zeng","orcid":"0000-0003-4885-4788","position":7,"is_corresponding":false},{"id":768893,"name":"Haiqing Huang","orcid":"0000-0002-8932-7995","position":8,"is_corresponding":false},{"id":530119,"name":"George Grove","orcid":"0000-0002-5043-139X","position":9,"is_corresponding":false},{"id":465018,"name":"Yijun Chen","orcid":"0000-0002-4920-152X","position":10,"is_corresponding":false},{"id":1205147,"name":"Tara K Lafferty","orcid":null,"position":11,"is_corresponding":false},{"id":425004,"name":"Anuradha Sehrawat","orcid":"0000-0002-7243-5447","position":12,"is_corresponding":false},{"id":544014,"name":"M. Ilyas Kamboh","orcid":"0000-0002-3453-1438","position":13,"is_corresponding":false},{"id":363262,"name":"Anna L. Marsland","orcid":"0000-0001-8951-7513","position":14,"is_corresponding":false},{"id":1212599,"name":"Arthur Kramer","orcid":"0000-0002-1991-5046","position":15,"is_corresponding":false},{"id":395469,"name":"Edward McAuley","orcid":"0000-0002-4574-3292","position":16,"is_corresponding":false},{"id":68016,"name":"Jeffrey M. Burns","orcid":"0000-0001-7609-8954","position":17,"is_corresponding":false},{"id":225313,"name":"Charles H. Hillman","orcid":"0000-0002-3722-5612","position":18,"is_corresponding":false},{"id":441662,"name":"Eric D. Vidoni","orcid":"0000-0001-5181-7131","position":19,"is_corresponding":false},{"id":271300,"name":"Chaeryon Kang","orcid":"0000-0001-9442-8515","position":20,"is_corresponding":false},{"id":225312,"name":"Kirk I. Erickson","orcid":"0000-0001-8736-981X","position":21,"is_corresponding":false},{"id":1212598,"name":"Kelsey R. Sewell","orcid":"0000-0002-3859-5017","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:47:50.575618Z","pmid":"40110626","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":[]}