{"doi":"10.1002/acn3.70227","title":"Plasma Proteomic Signatures for Alzheimer's Disease: Comparable Accuracy to <scp>ATN</scp> Biomarkers and Cross‐Platform Validation","abstract":"BACKGROUND: There is growing recognition of the potential of plasma proteomics for Alzheimer's Disease (AD) risk assessment and disease characterization. However, differences between proteomics platforms introduce uncertainties regarding cross-platform applicability. OBJECTIVE: We aimed to identify a detailed plasma biosignature for distinguishing AD from cognitively normal (CN) and another signature for classifying mild cognitive impairment (MCI) decliners and non-decliners. We also explored the cross-platform applicability of these models between two proteomic platforms. METHODS: Elastic net was performed on 190 plasma analytes measured using the Luminex xMAP platform in 566 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to model MCI stable/decliner and AD/CN classification. MCI decliner was defined as progression to AD during follow-up (mean 4.2 ± 3.2 years). External cross-platform validation was conducted with 1303 participants from the Spanish Ace study, using the SOMAscan 7k platform. RESULTS: An 11-analyte signature for distinguishing AD from CN achieved a 93.5% accuracy on ADNI and 95.2% on Ace. The ApoE and BNP proteins were the two most important contributors to the classifier. The MCI classification signature performed less well, with 65.9% accuracy on ADNI and 51.0% accuracy upon validation testing in Ace. DISCUSSION: Compared with prior proteomic-based studies on the same dataset, our findings attained higher specificity and sensitivity for AD classification while utilizing a smaller panel of analytes. We also confirmed the reliability and consistency of this signature within a different population from a different platform. The plasma proteomic platforms explored were, however, not sufficient to determine MCI decliners versus non-decliners.","journal":"Annals of Clinical and Translational Neurology","year":2025,"id":577870,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9432,"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":237201,"name":"Oliver Robinson","orcid":"0000-0002-4735-0468","position":1,"is_corresponding":false},{"id":7730,"name":"Christina M. Lill","orcid":"0000-0002-1903-6762","position":2,"is_corresponding":false},{"id":392423,"name":"Anna Matton","orcid":"0000-0002-7819-0495","position":3,"is_corresponding":false},{"id":17624,"name":"Raquel Puerta","orcid":"0000-0002-1191-5893","position":4,"is_corresponding":false},{"id":1487645,"name":"Pilar Sánz","orcid":null,"position":5,"is_corresponding":false},{"id":17633,"name":"Mercè Boada","orcid":"0000-0003-2617-3009","position":6,"is_corresponding":false},{"id":17638,"name":"Agustı́n Ruiz","orcid":"0000-0003-2633-2495","position":7,"is_corresponding":false},{"id":808946,"name":"Lefkos Middleton","orcid":"0000-0002-2176-403X","position":8,"is_corresponding":false},{"id":29928,"name":"the Alzheimer's Disease Neuroimaging Initiative","orcid":null,"position":9,"is_corresponding":false},{"id":803431,"name":"Ming-guang Hu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T02:58:16.148027Z","pmid":"41083424","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":[]}