Targeted Proteomic Biomarker Profiling Using NULISA in a cohort enriched with risk for Alzheimer’s Disease and Related Dementias

Structured Abstract INTRODUCTION Targeted proteomic assays may be useful for diagnosing and staging Alzheimer’s disease and related dementias (ADRD). We evaluated the performance of a 120-marker central nervous system (CNS) NUcleic acid-Linked Immuno-Sandwich Assay (NULISA) panel in samples spanning the AD spectrum. METHODS Cross-sectional plasma samples (n=252) were analyzed using Alamar’s NULISAseq CNS panel. ROC analyses demonstrated NULISAseq-pTau217 accuracy in detecting amyloid (A) and tau (T) PET positivity. Differentially expressed proteins were identified using volcano plots. RESULTS NULISAseq-pTau217 accurately classified A/T PET status with ROC AUCs of 0.92/0.86. pTau217 was upregulated in A+, T+, and impaired groups with log2-fold changes of 1.21, 0.57 and 4.63, respectively, compared to A-. Interestingly, pTDP43-409 was also upregulated in the impaired group and correlated with declining hippocampal volume and cognitive trajectories. DISCUSSION This study shows the potential of a targeted proteomics panel for characterizing brain changes pertinent to ADRD. The promising pTDP43-409 findings require further replication.