Plasma pyroglutamate-modified amyloid beta differentiates amyloid pathology.

Introduction: Pyroglutamate-modified amyloid β (Aβ) could be a biomarker for Aβ plaque pathology in the brain. An ultra-high-sensitive assay is needed for detecting Aβ.

Methods: Immunomagnetic reduction was used for quantification of Aβ in plasma from 46 participants. The concentrations of Aβ of these subjects were compared with F-florbetapir positron emission tomography (PET) images.

Results: Aβ concentration was 44.1 ± 28.2 fg/mL in PET- (n = 28) and 91.6 ± 54.6 fg/mL in PET+ (n = 18; < .05). The cutoff value of Aβ 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 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 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.