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Commonly used methods often require antibody modification or fluorescent labeling. Furthermore, subtle differences in protein sequences make it more challenging to detect and differentiate multiple biomarkers. This study introduces a novel nanopore\u2010based method for simultaneous, label\u2010free detection of key Alzheimer's disease (AD) biomarkers in biological samples. The technique enables distinguishable and ultrasensitive detection of amyloid\u2010beta peptides (A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    ,A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    ) amyloid precursor protein (APP\n                    <jats:sub>669\u2010711<\/jats:sub>\n                    ), and tubulin associated unit (Tau) proteins in cerebrospinal fluid and serum. The method successfully identifies AD biomarkers by directly detecting A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    in cerebrospinal fluid and can detect age\u2010dependent changes in A\u03b2 levels in AD mice models, demonstrating reliability comparable to established enzyme linked immunosorbent assay (ELISA) assays and brain plaque\u2010staining confocal imaging. Notably, this method achieves significant advancements in detecting 2.1 p\n                    <jats:sc>m<\/jats:sc>\n                    A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    and 1.5 p\n                    <jats:sc>m<\/jats:sc>\n                    APP\n                    <jats:sub>(669\u2010711)<\/jats:sub>\n                    , as well as 627 f\n                    <jats:sc>m<\/jats:sc>\n                    A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    in serum. This improvement in nanopore technology addresses the challenges of detecting A\u03b2 and Tau alterations in complex biological samples and differentiating between similar protein sequences. The study marks a significant advancement in the analysis of pathogenic proteins in physiological samples, also offering a powerful tool for AD research and diagnostics.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202405058","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T11:21:51Z","timestamp":1742988111000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Multianalyte Nanopore Detection of Alzheimer's Disease Biomarkers: A Label\u2010Free Platform with Improved Sensitivity and Range"],"prefix":"10.1002","volume":"14","author":[{"given":"Qianshan","family":"Liu","sequence":"first","affiliation":[{"name":"Chongqing Institute of Green and Intelligent Technology Chinese Academy of Sciences Chongqing School The University of Chinese Academy of Sciences (UCAS Chongqing)  Chongqing 400714 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Brain Cognition and Brain Disease Institute Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences  Shenzhen 518055 China"},{"name":"School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Chongqing Institute of Green and Intelligent Technology Chinese Academy of Sciences Chongqing School The University of Chinese Academy of Sciences (UCAS Chongqing)  Chongqing 400714 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Missouri  Columbia MO 65211 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhan","sequence":"additional","affiliation":[{"name":"Brain Cognition and Brain Disease Institute Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences  Shenzhen 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7404-4319","authenticated-orcid":false,"given":"Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"Chongqing Institute of Green and Intelligent Technology Chinese Academy of Sciences Chongqing School The University of Chinese Academy of Sciences (UCAS Chongqing)  Chongqing 400714 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32205-4"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac1029874"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2021.129863"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-01946-y"},{"key":"e_1_2_10_5_1","volume":"5","author":"Tao Q. 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