Comparison of the diagnostic performance of blood‐based biomarkers using two distinct commercially available assays in a prospective memory clinic cohort

Abstract

AbstractBackgroundBlood‐based biomarkers have recently emerged as minimally‐invasive, accessible and relatively inexpensive diagnostic and prognostic tools for people with cognitive impairment. Before being routinely implemented in clinical practice, the diagnostic performance of distinct commercially available assays should be studied in real‐world cohorts. We aimed to study and compare the diagnostic accuracy of different plasma biomarkers measured using two different assay platforms in a memory clinic cohort.MethodParticipants were selected from a prospective memory clinic cohort; all had Alzheimer’s disease (AD) CSF biomarkers performed. Plasma p‐tau181, GFAP and NfL were measured using Simoa (Quanterix), while plasma p‐tau181, Aβ1‐40 and Aβ1‐42 were quantified using Lumipulse G (Fujirebio). Clinical diagnoses were made according to published criteria, blinded to plasma biomarkers. Aβ status (‐/+) was defined by CSF Aβ concentration using local cutoffs.ResultOne hundred and ten participants were included (mean age [standard deviation] 66 [7.8] years, 56% women). Diagnostic categories included 10 cognitively unimpaired controls, 24 with suspected non‐neurodegenerative cause of cognitive impairment (SND), 53 AD, 9 Lewy body disease (LBD, 4 Aβ+) and 14 frontotemporal dementia (FTD, 1 Aβ+).Plasma p‐tau181Quanterix and Aβ1‐42/Aβ1‐40 had the highest diagnostic accuracy (Figure 1) to discriminate between SND and AD (AUC [CI] 0.94 [0.89‐0.99] and 0.94 [0.85‐1]), followed by GFAP (0.93 [0.87‐0.99]), p‐tau181Fujirebio (0.90 [0.82‐0.98]) and Aβ1‐42 (0.71 [0.58‐0.85]). Plasma NfL performed the best to differentiate FTD from SND and AD (AUC 0.95 [0.88‐1] and 0.85 [0.71‐0.99], respectively).For Aβ status discrimination (Figure 2), p‐tau181Quanterix had an AUC [CI] of 0.91 [0.85‐0.96], followed by p‐tau181Fujirebio (0.86 [0.79‐0.93]), Aβ1‐42/Aβ1‐40 (0.85 [0.76‐0.93]) and GFAP (0.84 [0.77‐0.92]) with no statistically significant differences in AUCs. Balanced (Youden index) cut‐offs were calculated to study diagnostic performance, resulting in sensitivities of 79‐83%, specificities of 74‐83% and accuracies of 76‐83%. No combination of plasma biomarkers resulted in a significantly increased discriminative accuracy for Aβ status. All plasma biomarkers were moderately correlated with p‐tau181Quanterix (ρ = 0.40‐0.75, Figure 3).ConclusionIn our cohort, p‐tau181Quanterix, p‐tau181Fujirebio, Aβ1‐42/Aβ1‐40 and GFAP had a high diagnostic performance to discriminate CSF‐defined Aβ status. Plasma NfL identified individuals with FTD. Further studies comparing different plasma biomarkers are needed before implementation in clinical practice.