High concordance between plasma amyloid β biomarkers by IP‐MALDI‐MS and visual assessment of amyloid PET

Background Abnormal amyloid-β (Aβ) deposition in the brain has been defined as earliest pathological change of Alzheimer disease (AD). We combined immunoprecipitation (IP) with MALDI-TOF MS to develop IP-MALDI-MS, which is an analytical technique for plasma Aβ. This previously revealed that APP669-711/Aβ1-42 ratio, Aβ1-40/Aβ1-42 and a combination these two biomarkers (a composite biomarker) human correlates highly SUVR obtained from amyloid PET (Nakamura et al., Nature, 2018). In this work, we validated concordance between Aβ by IP-MALDI-MS visual status independent dataset previous report. Method Plasma samples were 41 Aβ+ 55 Aβ- subjects classified using PIB tracer National Center Geriatrics Gerontology. Aβ-related peptides immunoprecipitated sample spiked stable isotope-labeled (SIL) Aβ1-38 beads coupled anti-Aβ antibody. After IP was performed times consecutively, eluted antibody applied MS. SIL-Aβ1-38 used internal standard normalizing intensity each peptide. ratio calculated those intensities then biomarker generated reported. Result significantly higher group than (p < 0.001). discriminated Aβ-PET positivity high AUC (92.8%), (95.7%) (95.8%). Furthermore, accuracy three 89.6-92.7% Aβ+/- classification. Conclusion Our results demonstrated status. The measurement can provide values associated positivity.