{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:43:12Z","timestamp":1790390592362,"version":"4.1.0"},"reference-count":116,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T00:00:00Z","timestamp":1572998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["SAF2016-75508-R"],"award-info":[{"award-number":["SAF2016-75508-R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>While Alzheimer\u2019s disease (AD) classical diagnostic criteria rely on clinical data from a stablished symptomatic disease, newer criteria aim to identify the disease in its earlier stages. For that, they incorporated the use of AD\u2019s specific biomarkers to reach a diagnosis, including the identification of A\u03b2 and tau depositions, glucose hypometabolism, and cerebral atrophy. These biomarkers created a new concept of the disease, in which AD\u2019s main pathological processes have already taken place decades before we can clinically diagnose the first symptoms. Therefore, AD is now considered a dynamic disease with a gradual progression, and dementia is its final stage. With that in mind, new models were proposed, considering the orderly increment of biomarkers and the disease as a continuum, or the variable time needed for the disease\u2019s progression. In 2011, the National Institute on Aging and the Alzheimer\u2019s Association (NIA-AA) created separate diagnostic recommendations for each stage of the disease continuum\u2014preclinical, mild cognitive impairment, and dementia. However, new scientific advances have led them to create a unifying research framework in 2018 that, although not intended for clinical use as of yet, is a step toward shifting the focus from the clinical symptoms to the biological alterations and toward changing the future diagnostic and treatment possibilities. This review aims to discuss the role of biomarkers in the onset of AD.<\/jats:p>","DOI":"10.3390\/ijms20225536","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T06:52:36Z","timestamp":1573109556000},"page":"5536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":118,"title":["When Does Alzheimer\u2032s Disease Really Start? The Role of Biomarkers"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0266-0304","authenticated-orcid":false,"given":"Ana","family":"Lloret","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Valencia, Health Research Institute INCLIVA, Avda. Blasco Ibanez, 17, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Esteve","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Valencia, Health Research Institute INCLIVA, Avda. Blasco Ibanez, 17, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Angeles","family":"Lloret","sequence":"additional","affiliation":[{"name":"Department of Clinic Neurophysiology. University Clinic Hospital of Valencia, Avda. Blasco Ibanez, 19, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Cervera-Ferri","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Embriology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Neurology. University Clinic Hospital of Valencia, Avda. Blasco Ibanez, 19, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Nepomuceno","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Valencia, Health Research Institute INCLIVA, Avda. Blasco Ibanez, 17, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Monllor","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Valencia, Health Research Institute INCLIVA, Avda. Blasco Ibanez, 17, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"356385","DOI":"10.1007\/BF02866241","article-title":"\u00dcber eigenartige Krankheitsf\u00e4lle des sp\u00e4teren Alters","volume":"4","author":"Alzheimer","year":"1911","journal-title":"Z. Gesamte Neurol. 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