{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:59:55Z","timestamp":1793501995306,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AG062715"],"award-info":[{"award-number":["P30 AG062715"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG027161"],"award-info":[{"award-number":["R01 AG027161"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG021155"],"award-info":[{"award-number":["R01 AG021155"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG054059"],"award-info":[{"award-number":["R01 AG054059"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Targeted proteomic assays may be useful for diagnosing and staging Alzheimer's disease and related dementias (ADRD). We evaluated the performance of a 120\u2010marker central nervous system (CNS) NUcleic acid Linked Immuno\u2010Sandwich Assay (NULISA) panel in samples spanning the Alzheimer's disease (AD) spectrum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Cross\u2010sectional plasma samples (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0252) were analyzed using NULISAseq CNS panel from Alamar Biosciences. Receiver\u2010operating characteristic (ROC) analyses demonstrated the accuracy from NULISAseq\u2010tau phosphorylated at threonine 217 (pTau217) in detecting amyloid (A) and tau (T) positron emission tomography (PET) positivity. Differentially expressed proteins were identified using volcano plots.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      NULISAseq\u2010pTau217 accurately classified A\/T PET status with ROC areas under the curve of 0.92\/0.86; pTau217 was upregulated in A+, T+, and impaired groups with log\n                      <jats:sub>2<\/jats:sub>\n                      \u2010fold changes of 1.21, 0.57, and 4.63, respectively, compared to A\u2212. Of interest, TAR DNA\u2010binding protein 43 (TDP\u201043) phosphorylated at serine 409 (pTDP43\u2010409) was also upregulated in the impaired group and correlated with declining hippocampal volume and cognitive trajectories.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>This study shows the potential of a targeted proteomics panel for characterizing brain changes pertinent to ADRD. The promising pTDP43\u2010409 findings require further replication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>The NULISAseq pTau217 assay was comparable to the Simoa pTau217 assay, both utilizing the ALZpath antibody, in detecting amyloid positron emission tomography (PET) positivity, each with areas under the curve greater than 90%.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Nineteen proteins were differentially expressed in participants with mild cognitive impairment (MCI) compared to those who were unimpaired. Markers of non\u2010AD proteinopathies such as pTDP43\u2010409, oligomeric alpha\u2010synuclein, and huntingtin (HTT), were among those upregulated in MCI.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>High levels of plasma pTDP43\u2010409 were associated with worsening hippocampal atrophy and cognitive decline, clinical indicators of limbic\u2010predominant age\u2010related TDP\u201043 encephalopathy (LATE), compared to those with low pTDP43\u2010409.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70166","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T10:00:44Z","timestamp":1746180044000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Targeted proteomic biomarker profiling using NULISA in a cohort enriched with risk for Alzheimer's disease and related dementias"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-282X","authenticated-orcid":false,"given":"Ramiro Eduardo","family":"Rea Reyes","sequence":"first","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael E.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca E.","family":"Langhough","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel L.","family":"Studer","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Institute University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin M.","family":"Jonaitis","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie E.","family":"Oomens","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Planalp","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara B.","family":"Bendlin","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel A.","family":"Chin","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Asthana","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"},{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology, Queen Square  London UK"},{"name":"UK Dementia Research Institute at UCL  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sterling C.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13859"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32205-4"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00403-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-022-01150-0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14262"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-024-02728-8"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42834-x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2017.11.007"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000223"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13774"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000111"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.688478"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_8_16_1","volume-title":"Rey Auditory Verbal Learning Test: A Handbook","author":"Schmidt M","year":"1996"},{"key":"e_1_2_8_17_1","volume-title":"Wechsler Memory Scale\u2014Revised","author":"Wechsler D","year":"1987"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.2466\/pms.1958.8.3.271"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.6669"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2018.11.006"},{"key":"e_1_2_8_21_1","first-page":"1","article-title":"Visual read of [F\u201018]florquinitau PET that includes and extends beyond the mesial temporal lobe is associated with increased plasma pTau217 and cognitive decline in a cohort that is enriched with risk for Alzheimer's disease","author":"Rea Reyes RE","year":"2024","journal-title":"Alzheimer's Dement"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.09.028"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.02.046"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-021-01282-8"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00109-6"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.10.11.24315349"},{"key":"e_1_2_8_27_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"Team RC","year":"2024"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v067.i01"},{"key":"e_1_2_8_30_1","article-title":"Emmeans: Estimated Marginal Means, aka Least\u2010Squares Means. 2024","author":"Lenth RV","journal-title":"R package version 1.10.1"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26711"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19980430)17:8<857::AID-SIM777>3.0.CO;2-E"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.07.29.24311079"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.08.22.24312244"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.06.13.24308895"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-024-00753-5"},{"key":"e_1_2_8_37_1","article-title":"A comprehensive head\u2010to\u2010head comparison of key plasma phosphorylated tau 217 biomarker tests","volume":"2","author":"Warmenhoven N","year":"2024","journal-title":"Brain"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.5319"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105046"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.10.26.24316176"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2022-330540"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-021-02275-6"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab223"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-022-01058-9"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00463"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.302072"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001831"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2014.3736"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.194"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2019.7762"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.663637"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-023-04687-x"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1586\/erm.12.5"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70166","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.70166","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70166","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:32:53Z","timestamp":1789558373000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/alz.70166"],"URL":"https:\/\/doi.org\/10.1002\/alz.70166","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.11.28.24318162","asserted-by":"object"}]},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"2024-11-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70166"}}