Plasma vs. serum: which is better for proteomic blood biomarker analysis? Evaluation of the novel NULISA platform

STRUCTURED ABSTRACTO_ST_ABSINTRODUCTIONC_ST_ABSThe NULISASeq CNS Disease Panel has high potential for AD diagnosis, but the comparability of serum vs. plasma remains unclear. METHODSWe compared its performance on 43 matched serum-plasma pairs from a memory clinic cohort. RESULTSThe panel reproducibly quantified 124 targets (mean CV=4.9%) with high detectability (mean=95.7%). Serum-plasma correlations were strong ({rho}>0.7) for 79 targets. 48 targets had significant NPQ differences, with 32 higher in plasma. Plasma had more erythrocyte-enriched proteins (HBA1, PGK1, SOD1, PRDX6), while serum had more platelet-derived proteins (CD40LG, BDNF, VEGFA, A{beta}40). For classical AD biomarkers, serum-plasma correlations were stronger for p-tau, GFAP, and NfL ({rho}>0.9) than for A{beta} targets ({rho}=0.594- 0.785). Tau levels were higher in plasma; GFAP and NfL were similar, and A{beta} peptides were mixed. Twelve targets, along with p-tau217/A{beta}42, were linked to AD diagnosis, with plasma generally showing stronger effects. DISCUSSIONOur results support serum use but suggest plasma performs better for AD using this panel.