Plasma pyroglutamate‐modified amyloid beta differentiates amyloid pathology

Abstract

Abstract Introduction Pyroglutamate‐modified amyloid β (AβpE3) could be a biomarker for Aβ plaque pathology in the brain. An ultra‐high‐sensitive assay is needed for detecting AβpE3‐40. Methods Immunomagnetic reduction was used for quantification of AβpE3‐40 in plasma from 46 participants. The concentrations of AβpE3‐40 of these subjects were compared with 18F‐florbetapir positron emission tomography (PET) images. Results AβpE3‐40 concentration was 44.1 ± 28.2 fg/mL in PET‐ (n = 28) and 91.6 ± 54.6 fg/mL in PET+ (n = 18; P < .05). The cutoff value of AβpE3‐40 for discriminating PET‐ from PET+ was 55.5 fg/mL, resulting in a sensitivity of 83.3%, a specificity of 71.4%. The concentration of AβpE3‐40 showed a moderate correlation (r = 0.437) with PET standardized uptake value ratio. Discussion We did not enroll pre‐clinical AD subject with normal cognition but Aβ PET+. It would be an important issue to explore the feasibility of using AβpE3‐40 for screening pre‐clinical subjects. Conclusion These results reveal the feasibility of detecting Aβ pathology using quantification of a plaque‐derived Aβ molecule in plasma.