Wang, P-N; Lin, K-J; Liu, H-C; Andreasson, U; Blennow, K; Zetterberg, H; Yang, S-Y; (2020) Plasma pyroglutamate-modified amyloid beta differentiates amyloid pathology. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring , 12 (1) , Article e12029. 10.1002/dad2.12029.

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Abstract

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: mmunomagnetic 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 18F‐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.

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