Novel plasma biomarkers of amyloid plaque pathology and cortical thickness: evaluation of the NULISA targeted proteomic platform in an ethnically diverse cohort
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INTRODUCTION
Proteomic evaluation of plasma samples could accelerate the identification of novel Alzheimer’s disease (AD) biomarkers. We evaluated the novel NUcleic acid Linked Immuno-Sandwich Assay (NULISA TM ) proteomic method in an ethnically diverse cohort.
METHODS
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.
RESULTS
On NULISA, phosphorylated tau (p-tau217, p-tau231, p-tau181), GFAP, and MAPT-tau showed the top significant association with Aβ PET status, followed by neuroinflammation markers CCL2, CHIT1, CXCL8, and the synaptic marker NRGN. Biomarkers associated with cortical thickness included astrocytic protein CHI3L1, cytokine CD40LG, growth factor BDNF, Aβ-associated metalloprotein TIMP3, and FCN2 linked with brain atrophy in AD. Furthermore, moderate to strong between-platform correlations were observed for various assays.
DISCUSSION
NULISA multiplexing advantage allowed concurrent assessment of established and novel plasma biomarkers of Aβ pathology and neurodegeneration.
