{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T02:48:35Z","timestamp":1788576515920,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T00:00:00Z","timestamp":1593129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Neuronal extracellular vesicle (nEV) tau and insulin signaling biomarkers may detect preclinical Alzheimer's disease and age\u2010associated cognitive decline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This case\u2010control study used repeated serum samples from 73 cognitively declining and 73 stable Wisconsin Registry for Alzheimer's Prevention participants (62.4 \u00b1 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Declining compared to stable individuals showed higher baseline total, p231\u2010, and p181\u2010tau with older age and higher annualized change for p\u2010IR and p\u2010IGF\u20101R. 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Combining nEV biomarkers can identify individuals with age\u2010associated cognitive decline.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12130","type":"journal-article","created":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T03:38:55Z","timestamp":1593229135000},"page":"1293-1304","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Extracellular vesicle biomarkers of Alzheimer's disease associated with sub\u2010clinical cognitive decline in late middle age"],"prefix":"10.1002","volume":"16","author":[{"given":"Erden","family":"Eren","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Investigation Intramural Research Program National Institute on Aging NIH  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack F. 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