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

Pei Ning Wang
, Kun Ju Lin
, Huei Chun Liu
, Ulf Andreasson
, Kaj Blennow
, Henrik Zetterberg
, Shieh Yueh Yang^*

^*此作品的通信作者

Veterans General Hospital-Taipei
National Yang Ming Chiao Tung University
Chang Gung Memorial Hospital
Chang Gung University
MagQu Co., Ltd.
University of Gothenburg
Sahlgrenska University Hospital
University College London

研究成果: 期刊稿件 › 文章 › 同行評審

11 引文斯高帕斯（Scopus）

摘要

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.

原文	英語
文章編號	e12029
期刊	Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
卷	12
發行號	1
DOIs	https://doi.org/10.1002/dad2.12029
出版狀態	已出版 - 2020
對外發佈	是

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© 2020 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of the Alzheimer's Association.

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10.1002/dad2.12029

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title = "Plasma pyroglutamate-modified amyloid beta differentiates amyloid pathology",

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.",

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AU - Wang, Pei Ning

AU - Lin, Kun Ju

AU - Liu, Huei Chun

AU - Andreasson, Ulf

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Yang, Shieh Yueh

PY - 2020

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N2 - 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.

AB - 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.

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M3 - 文章

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Plasma pyroglutamate-modified amyloid beta differentiates amyloid pathology

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