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

medRxiv [Preprint]. 2024 Nov 29:2024.11.28.24318162. doi: 10.1101/2024.11.28.24318162.

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.

PMID:39649596 | PMC:PMC11623751 | DOI:10.1101/2024.11.28.24318162