Novel plasma biomarkers of amyloid plaque pathology and cortical thickness: Evaluation of the NULISA targeted proteomic platform in an ethnically diverse cohort

Classical Alzheimer's disease (AD) biomarkers measured using the NUcleic acid Linked Immuno-Sandwich Assay (NULISA) with next-generation 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. NULISAseq proteomic analysis identified several plasma biomarkers strongly associated with AD pathology in a biracial community cohort of older adults. Notably, phosphorylated tau-217 (p-tau217), GFAP, and p-tau231 displayed the strongest association with amyloid beta (Aβ) pathology, whereas brain-derived neurotrophic factor (BDNF) was strongly associated with neurodegeneration. We demonstrate that plasma biomarker levels could be influenced by age, sex, apolipoprotein E (APOE) genotype, and self-identified race. Specifically, GFAP, NfL, and surfactant protein D (SFTPD) showed a strong association with age; CD63 and S100 calcium-binding protein B (S100B) with self-identified race; synaptosomal-associated protein 25 (SNAP25) with APOE genotype; and serum amyloid A1 (SAA1) and superoxide dismutase 1 (SOD1) with significant sex differences.