{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:27:58Z","timestamp":1785929278139,"version":"3.56.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T00:00:00Z","timestamp":1704672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG067607"],"award-info":[{"award-number":["R01 AG067607"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005562","name":"North Carolina Biotechnology Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005562","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is characterized by a long preclinical phase. Although late-stage AD\/dementia may be robustly differentiated from cognitively normal individuals by means of a clinical evaluation, PET imaging, and established biofluid biomarkers, disease differentiation between cognitively normal and various subtypes of mild cognitive impairment (MCI) remains a challenging task. Differential biomarkers for early-stage AD diagnosis with accessible biofluid samples are urgently needed. Misfolded phosphorylated tau aggregates (p-tau) are present in multiple neurodegenerative diseases known as \u201ctauopathies\u201d, with the most common being AD. P-tau181 is a well-established p-tau biomarker to differentiate AD dementia from non-AD pathology. However, it is unclear if p-tau181 is capable of diagnosing MCI, an early AD stage, from cognitively normal subjects, or if it can discriminate MCI subtypes amnestic MCI (aMCI) from non-amnestic MCI (naMCI). Here we evaluated the capability of p-tau181 in diagnosing MCI from cognitively normal subjects and discriminating aMCI from naMCI subtypes. We collected matching plasma and CSF samples of a clinically diagnosed cohort of 35 cognitively normal, 34 aMCI, 17 naMCI, and 31 AD dementia cases (total 117 participants) with supplemental CSF A\u03b242 and total tau AD biomarker levels and performed Simoa p-tau181 assays. The diagnostic capabilities of Simoa p-tau181 assays to differentiate these cohorts were evaluated. We found (i) p-tau181 can robustly differentiate MCI or aMCI from cognitively normal cohorts with matching plasma and CSF samples, but such differentiation is weaker in diagnosing naMCI from cognitively normal groups, (ii) p-tau181 is not capable of differentiating aMCI from naMCI cohorts, and (iii) either factor of A\u03b2 or total tau burden markedly improved differentiation power to diagnose aMCI from cognitively normal group. Plasma and CSF p-tau181 levels may serve as a promising biomarker for diagnosing aMCI from normal controls in the preclinical phase. But more robust new biomarkers are needed to differentiate naMCI from cognitively normal cases or to discriminate between MCI subtypes, aMCI from naMCI.<\/jats:p>","DOI":"10.3389\/fnmol.2023.1288930","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T04:12:35Z","timestamp":1704687155000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Differential diagnosis of mild cognitive impairment of Alzheimer\u2019s disease by Simoa p-tau181 measurements with matching plasma and CSF"],"prefix":"10.3389","volume":"16","author":[{"given":"Ling","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Arvai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Hsiu J.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy J.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.cell.2020.01.027","article-title":"Posttranslational modifications mediate the structural diversity of tauopathy strains.","volume":"180","author":"Arakhamia","year":"2020","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.103836","article-title":"Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer\u2019s disease.","volume":"76","author":"Ashton","year":"2022","journal-title":"EBioMedicine"},{"key":"B3","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1007\/s00401-021-02275-6","article-title":"Plasma p-tau231: a new biomarker for incipient Alzheimer\u2019s disease pathology.","volume":"141","author":"Ashton","year":"2021","journal-title":"Acta Neuropathol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.jalz.2014.02.004","article-title":"Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer\u2019s disease.","volume":"11","author":"Blennow","year":"2015","journal-title":"Alzheimers Dement."},{"key":"B5","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological staging of Alzheimer-related changes.","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.942629","article-title":"Plasma tau proteins for the diagnosis of mild cognitive impairment and Alzheimer\u2019s disease: A systematic review and meta-analysis.","volume":"14","author":"Chen","year":"2022","journal-title":"Front. 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