Plasma pyroglutamate-modified amyloid beta differentiates amyloid pathology

Pei-Ning Wang; Kun-Ju Lin; Huei-Chun Liu; Ulf Andreasson; Kaj Blennow; Henrik Zetterberg; Shieh-Yueh Yang

doi:10.1002/dad2.12029

Plasma pyroglutamate-modified amyloid beta differentiates amyloid pathology

Alzheimers Dement (Amst). 2020 Apr 30;12(1):e12029. doi: 10.1002/dad2.12029. eCollection 2020.

Authors

Pei-Ning Wang^{1

2

3}, Kun-Ju Lin^{4

5}, Huei-Chun Liu⁶, Ulf Andreasson^{7

8}, Kaj Blennow^{7

8}, Henrik Zetterberg^{7

8

9

10}, Shieh-Yueh Yang^{6

11}

Affiliations

¹ Department of Neurology Neurological Institute Taipei Veterans General Hospital Taipei Taiwan.
² Department of Neurology School of Medicine National Yang-Ming University Taipei Taiwan.
³ Brain Research Center National Yang-Ming University Taipei Taiwan.
⁴ Department of Nuclear Medicine and Molecular Imaging Center Linkou Chang Gung Memorial Hospital Tao-Yuan Taiwan.
⁵ Healthy Aging Research Center and Department of Medical Imaging and Radiological Sciences College of Medicine, Chang Gung University Tao-Yuan Taiwan.
⁶ MagQu Co., Ltd. New Taipei City Taiwan.
⁷ Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden.
⁸ Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden.
⁹ Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology, Queen Square London UK.
¹⁰ UK Dementia Research Institute at UCL London UK.
¹¹ MagQu LLC Surprise Arizona USA.

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: 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 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.