{"doi":"10.1002/alz.12130","title":"Extracellular vesicle biomarkers of Alzheimer's disease associated with sub‐clinical cognitive decline in late middle age","abstract":"INTRODUCTION: Neuronal extracellular vesicle (nEV) tau and insulin signaling biomarkers may detect preclinical Alzheimer's disease and age-associated cognitive decline. METHODS: This case-control study used repeated serum samples from 73 cognitively declining and 73 stable Wisconsin Registry for Alzheimer's Prevention participants (62.4 ± 6.3 years old). We immunocaptured nEVs; measured tau and insulin signaling biomarkers; and examined biomarker differences by group, their performance in group classification in training and test datasets (97, 49 individuals, respectively), and whether they predict cognitive performance change. RESULTS: Declining compared to stable individuals showed higher baseline total, p231-, and p181-tau with older age and higher annualized change for p-IR and p-IGF-1R. Combining biomarkers classified decliners with 94% area under the curve (AUC), 86.0% sensitivity and 86.7% specificity, in training data, and 75% AUC, 71.4% sensitivity, and 77.3% specificity, in test data. Insulin biomarkers predicted cognitive performance change prospectively. DISCUSSION: Combining nEV biomarkers can identify individuals with age-associated cognitive decline.","journal":"Alzheimer s & Dementia","year":2020,"id":56072,"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":88,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8816,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":291166,"name":"Jack F.V. Hunt","orcid":"0000-0002-5719-9028","position":1,"is_corresponding":false},{"id":36350,"name":"Michelle Shardell","orcid":"0000-0002-5283-2082","position":2,"is_corresponding":false},{"id":293368,"name":"Sahil Chawla","orcid":null,"position":3,"is_corresponding":false},{"id":293369,"name":"Joyce Tran","orcid":null,"position":4,"is_corresponding":false},{"id":291167,"name":"Jeffrey Gu","orcid":"0000-0001-8854-0738","position":5,"is_corresponding":false},{"id":293370,"name":"Nick M. Vogt","orcid":null,"position":6,"is_corresponding":false},{"id":230038,"name":"Sterling C. Johnson","orcid":"0000-0002-8501-545X","position":7,"is_corresponding":false},{"id":291168,"name":"Barbara B. Bendlin","orcid":"0000-0002-0580-9875","position":8,"is_corresponding":false},{"id":256661,"name":"Dimitrios Kapogiannis","orcid":"0000-0003-2181-3118","position":9,"is_corresponding":false},{"id":281923,"name":"Erden Eren","orcid":"0000-0002-5190-9500","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T21:05:49.581291Z","pmid":"32588967","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":[]}