{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:45:37Z","timestamp":1792842337774,"version":"4.5.0"},"reference-count":37,"publisher":"Walter de Gruyter GmbH","issue":"2","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"crossref","award":["860197"],"award-info":[{"award-number":["860197"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100013301","name":"Parkinson\u2019s Foundation","doi-asserted-by":"crossref","award":["PF-PRF-934916"],"award-info":[{"award-number":["PF-PRF-934916"]}],"id":[{"id":"10.13039\/100013301","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_cclm-2023-0659_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Decreased cerebrospinal fluid (CSF) amyloid beta 42\/40 ratio (A\u03b242\/40) is one of the core Alzheimer\u2019s disease (AD) biomarkers. Measurement of A\u03b242\/40 in plasma has also been proposed as a surrogate marker for amyloidosis, however the validity and the diagnostic performance of this biomarker is still uncertain. Here we evaluated two immunoassays targeting distinct regions of the amyloid peptides by (a)\u00a0performing a method comparison in both CSF and plasma, and (b)\u00a0assessing the diagnostic performance across the AD continuum.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2023-0659_abs_002\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used N4PE and N3PA Simoa<jats:sup>\u00ae<\/jats:sup> assays to measure A\u03b242\/40 in CSF and plasma of 134 patients: preclinical AD (pre-AD, n=19), mild cognitive impairment due to AD (MCI-AD, n=41), AD at the dementia stage (AD-dem, n=35), and a control group (CTRL, n=39). The N4PE includes a detector antibody targeting the amyloid N-terminus, while the N3PA uses a detector targeting amyloid mid-region.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2023-0659_abs_003\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Method comparison of N4PE and N3PA assays revealed discrepancies in assessment of plasma A\u03b242\/A\u03b240. While the diagnostic performance of the two assays did not significantly differ in CSF, in plasma, N4PE assay provided better accuracy for AD discrimination than N3PA assay (AUC\u00a0AD-dem vs. CTRL 0.77 N4PE, 0.68 N3PA).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2023-0659_abs_004\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>While both A\u03b242\/40 assays allowed for an effective discrimination between CTRL and different AD stages, the assay targeting amyloid N-terminal region provided the best diagnostic performance in plasma. Differences observed in technical and diagnostic performance of the two assays may depend on matrix-specific amyloid processing, suggesting that further studies should be carried to standardize amyloid ratio measurement in plasma.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/cclm-2023-0659","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T13:28:12Z","timestamp":1693574892000},"page":"332-340","source":"Crossref","is-referenced-by-count":23,"title":["CSF and plasma A\u03b242\/40 across Alzheimer\u2019s disease continuum: comparison of two ultrasensitive Simoa<sup>\u00ae<\/sup> assays targeting distinct amyloid regions"],"prefix":"10.1515","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6958-8223","authenticated-orcid":false,"given":"Anna Lidia","family":"Wojda\u0142a","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Neurochemistry, Section of Neurology, Department of Medicine and Surgery , University of Perugia , Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-5650","authenticated-orcid":false,"given":"Giovanni","family":"Bellomo","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Neurochemistry, Section of Neurology, Department of Medicine and Surgery , University of Perugia , Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Toja","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Neurochemistry, Section of Neurology, Department of Medicine and Surgery , University of Perugia , Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Gaetani","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Neurochemistry, Section of Neurology, Department of Medicine and Surgery , University of Perugia , Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucilla","family":"Parnetti","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Neurochemistry, Section of Neurology, Department of Medicine and Surgery , University of Perugia , Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1169-3258","authenticated-orcid":false,"given":"Davide","family":"Chiasserini","sequence":"additional","affiliation":[{"name":"Section of Physiology and Biochemistry, Department of Medicine and Surgery , University of Perugia , Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"2024030716382278870_j_cclm-2023-0659_ref_001","doi-asserted-by":"crossref","unstructured":"Jack, CR, Bennett, DA, Blennow, K, Carrillo, MC, Dunn, B, Haeberlein, SB, et al.. 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Comparison of ELISA- and SIMOA-based quantification of plasma A\u03b2 ratios for early detection of cerebral amyloidosis. Alzheimer\u2019s Res Ther 2020;12:162. https:\/\/doi.org\/10.1186\/s13195-020-00728-w.","DOI":"10.1186\/s13195-020-00728-w"},{"key":"2024030716382278870_j_cclm-2023-0659_ref_023","doi-asserted-by":"crossref","unstructured":"Thijssen, EH, Verberk, IMW, Vanbrabant, J, Koelewijn, A, Heijst, H, Scheltens, P, et al.. Highly specific and ultrasensitive plasma test detects Abeta(1-42) and Abeta(1-40) in Alzheimer\u2019s disease. Sci Rep 2021;11:9736. https:\/\/doi.org\/10.1038\/s41598-021-89004-x.","DOI":"10.1038\/s41598-021-89004-x"},{"key":"2024030716382278870_j_cclm-2023-0659_ref_024","doi-asserted-by":"crossref","unstructured":"Boulo, S, Kuhlmann, J, Andreasson, U, Brix, B, Venkataraman, I, Herbst, V, et al.. First amyloid \u03b21-42 certified reference material for re-calibrating commercial immunoassays. 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Improving the accuracy, robustness, and dynamic range of digital bead assays. 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