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We evaluated the novel NUcleic acid Linked Immuno\u2010Sandwich Assay (NULISA) proteomic method in an ethnically diverse cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Plasma biomarkers were measured with NULISA in the Human Connectome Project, a predominantly preclinical biracial community cohort in southwestern Pennsylvania. Selected biomarkers were additionally measured using Simoa and Quest immunoassays and compared.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>On NULISA, phosphorylated tau (p\u2010tau217, p\u2010tau231, and p\u2010tau181), glial fibrillary acidic protein (GFAP), and microtubule\u2010associated protein tau (MAPT\u2010tau) showed the top significant association with amyloid beta (A\u03b2) positron emission tomography (PET) status, followed by the neuroinflammation markers C\u2010C motif ligand 2 (CCL2), chitotriosidase 1 (CHIT1) and interleukin\u20108 (CXCL8), and the synaptic marker neurogranin (NRGN). Biomarkers associated with cortical thickness included astrocytic protein chitinase\u20103\u2010like protein 1 (CHI3L1), cytokine CD40 ligand (CD40LG), brain\u2010derived neurotrophic factor (BDNF), the A\u03b2\u2010associated metalloprotein TIMP3 (tissue inhibitor of metalloprotein 3), and ficolin 2 (FCN2). Furthermore, moderate to strong between\u2010platform correlations were observed for various assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>NULISA multiplexing advantage allowed concurrent assessment of established and novel plasma biomarkers of A\u03b2 pathology and neurodegeneration.<\/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>Classical Alzheimer's disease (AD) biomarkers measured using the NUcleic acid Linked Immuno\u2010Sandwich Assay (NULISA) with next\u2010generation sequencing readout (NULISAseq) CNS panel showed strong concordance with those measured using established immunoassay methods from Quanterix and Quest, with glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) exhibiting the strongest correlation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>NULISAseq proteomic analysis identified several plasma biomarkers strongly associated with AD pathology in a biracial community cohort of older adults. Notably, phosphorylated tau\u2010217 (p\u2010tau217), GFAP, and p\u2010tau231 displayed the strongest association with amyloid beta (A\u03b2) pathology, whereas brain\u2010derived neurotrophic factor (BDNF) was strongly associated with neurodegeneration.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            We demonstrate that plasma biomarker levels could be influenced by age, sex, apolipoprotein E (\n                            <jats:italic>APOE<\/jats:italic>\n                            ) genotype, and self\u2010identified race. Specifically, GFAP, NfL, and surfactant protein D (SFTPD) showed a strong association with age; CD63 and S100 calcium\u2010binding protein B (S100B) with self\u2010identified race; synaptosomal\u2010associated protein 25 (SNAP25) with\n                            <jats:italic>APOE<\/jats:italic>\n                            genotype; and serum amyloid A1 (SAA1) and superoxide dismutase 1 (SOD1) with significant sex differences.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14535","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T05:45:47Z","timestamp":1740375947000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Novel plasma biomarkers of amyloid plaque pathology and cortical thickness: Evaluation of the NULISA targeted proteomic platform in an ethnically diverse cohort"],"prefix":"10.1002","volume":"21","author":[{"given":"Xuemei","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Psychiatry School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Sehrawat","sequence":"additional","affiliation":[{"name":"Department of Psychiatry School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara K.","family":"Lafferty","sequence":"additional","affiliation":[{"name":"Department of Psychiatry School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahika","family":"Rawat","sequence":"additional","affiliation":[{"name":"Department of Psychiatry School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Ilyas","family":"Kamboh","sequence":"additional","affiliation":[{"name":"Department of Human Genetics School of Public Health University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor L.","family":"Villemagne","sequence":"additional","affiliation":[{"name":"Department of Psychiatry School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar L.","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann D.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1422-4358","authenticated-orcid":false,"given":"Thomas K.","family":"Karikari","sequence":"additional","affiliation":[{"name":"Department of Psychiatry School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010022\u201000665\u20102"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010023\u201000605\u20108"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/yco.0000000000000851"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.34.7.939"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(06)69113\u20107"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm10030116"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51681"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/rlu.0000000000000547"},{"issue":"3","key":"e_1_2_8_10_1","first-page":"239","article-title":"A review of neuroimaging biomarkers of Alzheimer's disease","volume":"18","author":"Varghese T","year":"2013","journal-title":"Neurol Asia"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010024\u201000711\u20101"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25456"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.06.2266"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab223"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010024\u201001513\u20109"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad267"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702\u2010020\u201002232\u20109"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000271090.28148.24"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab099"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2023.53"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010023\u201001155\u2010w"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201042834\u2010x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010024\u201000753\u20105"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14413"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.669490"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.02.024"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20009"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000005549"},{"key":"e_1_2_8_29_1","unstructured":"Interleukin\u20106 (IL\u20106) Serum.Diagnostics Q. 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