Plasma pyroglutamate-modified amyloid beta differentiates amyloid pathology.

INTRODUCTION: Pyroglutamate-modified amyloid β (Aβ(pE3)) could be a biomarker for Aβ plaque pathology in the brain. An ultra-high-sensitive assay is needed for detecting Aβ(pE3-40). METHODS: Immunomagnetic reduction was used for quantification of Aβ(pE3-40) in plasma from 46 participants. The concentrations of Aβ(pE3-40) of these subjects were compared with (18)F-florbetapir positron emission tomography (PET) images. RESULTS: Aβ(pE3-40) 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 Aβ(pE3-40) 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 Aβ(pE3-40) 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 Aβ(pE3-40) 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.