Head‐to‐head comparison of plasma biomarkers across the AD continuum in an Australian population

Background Plasma amyloid-β (Aβ) 1-42/Aβ1-40 ratio, phosphorylated-tau181 (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light (NFL) are putative blood-based biomarkers for Alzheimer’s disease (AD). However, head-to-head comparisons of the afore-mentioned across AD continuum lacking. Method Aβ1-42, Aβ1-40, p-tau181, GFAP NFL were measured using Single Molecule Array platform compared cross-sectionally in models with without risk factors (age, sex APOE ε4 status) Aβ PET positive confirmed participants (CU Aβ+, n = 39; MCI 33; 46) negative Aβ-, 81; 26) from Australian Imaging, Biomarker & Lifestyle Flagship Study Ageing (AIBL) cohort. Area under receiver operating characteristic curves (AUCs) predicting PET-/+ status DeLong test. Associations between plasma biomarker levels at baseline prospective cognitive decline (CDR-SOB) brain load also assessed. Result Lower Aβ1-42/Aβ1-40 ratio higher p-tau181 observed preclinical (Aβ1-42/Aβ1-40 ratio: ∼19%; p-tau181: ∼70%; GFAP: ∼52%), prodromal ∼14%; ∼69%; ∼45%) ∼16%; ∼91%; ∼85%), was (∼27%) (∼45%) (Figure 1). Based on AUCs, performed equivalent to or better than (≥) other biomarkers, (p-tau AUCs CU Aβ- vs Aβ+ ∼81%/ ∼86%/ ∼92%). A panel ≥ alone (biomarker 90%/ 89%/ 96%). Higher (β 0.531, p 3.18E-08), 0.530, 5.07E-08) 0.487, 4.76E-06) associated prospectively lower -6.035, 1.56E-04) 2.823, 4.72E-05) 2.075, 0.003) increased prospectively. Conclusion These findings suggest that altered