{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T16:58:29Z","timestamp":1784912309661,"version":"3.55.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Plasma biomarker has the potential to be the reliable and propagable approach in the early stage diagnosis of Alzheimer\u2019s disease (AD). However, conventional methods appear powerless in the detection of these biomarkers at low concentrations in plasma. Here, we determined plasma biomarker concentrations of patients across the AD spectrum by an improved digital enzyme-linked immunosorbent assay (ELISA) technique. Confirms the predictive and diagnostic value of this method for AD patients and study the relationships between these biomarkers and cognitive status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Plasma concentrations of amyloid-beta 40 (A\u03b240), amyloid-beta 42 (A\u03b242) and plasma phosphorylated tau at threonine 181 (p-tau181) were determined in 43\u2009AD patients, 33 mild cognitive impairment (MCI) patients and 40 normal cognition (NC) subjects as healthy controls using the improved digital ELISA technique. In addition, all subjects were required to receive neuropsychological assessments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Plasma p-tau181 level showed certain discrepancies between NC and MCI (<jats:italic>p\u2009&amp;lt;<\/jats:italic> 0.05), AD (<jats:italic>p\u2009&amp;lt;<\/jats:italic> 0.01) groups. The level of plasma A\u03b242 (<jats:italic>p\u2009&amp;lt;<\/jats:italic> 0.05) and A\u03b240 (<jats:italic>p\u2009&amp;lt;<\/jats:italic> 0.01) was significantly different between AD and NC group. The p-tau181 level was able to distinguish AD (AUC\u2009=\u20090.8768) and MCI (AUC\u2009=\u20090.7932) from NC with higher accuracy than A\u03b242\/A\u03b240 ratio (AUC\u2009=\u20090.8343, AUC\u2009=\u20090.6569). Both p-tau181 (CDR: <jats:italic>r<\/jats:italic>\u2009=\u20090.388 <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001; MMSE: <jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.394 <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001) and A\u03b242\/A\u03b240 ratio (CDR: <jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.413 <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001; MMSE: <jats:italic>r<\/jats:italic>\u2009=\u20090.358 <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001) showed stronger positive correlation with clinical dementia rating (CDR) and mini mental state examination (MMSE) scores than A\u03b242 (CDR: <jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.280 <jats:italic>p<\/jats:italic>\u2009=\u20090.003; MMSE: <jats:italic>r<\/jats:italic>\u2009=\u20090.266 <jats:italic>p<\/jats:italic>\u2009=\u20090.005) or A\u03b240 (CDR: <jats:italic>r<\/jats:italic>\u2009=\u20090.373 <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001; MMSE: <jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.288 <jats:italic>p<\/jats:italic>\u2009=\u20090.002) alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Plasma p-tau181 level and A\u03b242\/A\u03b240 ratio showed promising values in diagnosis of AD and MCI. Our results indicate that this improved digital ELISA diagnosis approach can facilitate early recognition and management of AD and pre-AD patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1445479","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T04:35:42Z","timestamp":1725251742000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Highly sensitive blood-based biomarkers detection of beta-amyloid and phosphorylated-tau181 for Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"15","author":[{"given":"Wei","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulin","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangli","family":"Shou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanli","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"ref1","volume-title":"World 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