Evaluation of Blood-Based Plasma Biomarkers as Potential Markers of Amyloid Burden in Preclinical Alzheimer’s Disease

Author:

Winston Charisse N.1,Langford Oliver2,Levin Natalie1,Raman Rema2,Yarasheski Kevin3,West Tim3,Abdel-Latif Sara2,Donohue Michael2,Nakamura Akinori4,Toba Kenji56,Masters Colin L.7,Doecke James8,Sperling Reisa A.9,Aisen Paul S.2,Rissman Robert A.110

Affiliation:

1. Department of Neurosciences, University of California San Diego, La Jolla, CA, USA

2. Alzheimer’s Therapeutic Research Institute, Keck School of Medicine University of Southern California, San Diego, CA, USA

3. C N Diagnostics, St. Louis, MO, USA

4. Department of Biomarker Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan

5. National Center for Geriatrics and Gerontology, Obu, Aichi, Japan

6. Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

7. The Florey Institute, The University of Melbourne, Parkville, VIC, Australia

8. The Commonwealth Scientific and Industrial Research Organization, Brisbane, QLD, Australia

9. Harvard Medical School, Boston, MA, USA

10. Department of Neurosciences, University of California San Diego and VA San Diego Healthcare System, La Jolla, CA, USA

Abstract

Background: Participant eligibility for the A4 Study was determined by amyloid PET imaging. Given the disadvantages of amyloid PET imaging in accessibility and cost, blood-based biomarkers may serve as a sufficient biomarker and more cost-effective screening tool for patient enrollment into preclinical AD trials. Objective: To determine if a blood-based screening test can adequately identify amyloid burden in participants screened into a preclinical AD trial. Methods: In this cross-sectional study, 224 participants from the A4 Study received an amyloid PET scan (18Florbetapir) within 90 days of blood sample collection. Blood samples from all study participants were processed within 2 h after phlebotomy. Plasma amyloid measures were quantified by Shimazdu and C2 N Diagnostics using mass spectrometry-based platforms. A corresponding subset of blood samples (n = 100) was processed within 24 h after phlebotomy and analyzed by C2 N. Results: Plasma Aβ42/Aβ40 demonstrated the highest association for Aβ accumulation in the brain with an AUC 0.76 (95%CI = 0.69, 0.82) at C2 N and 0.80 (95%CI = 0.75, 0.86) at Shimadzu. Blood samples processed to plasma within 2 h after phlebotomy provided a better prediction of amyloid PET status than blood samples processed within 24 h (AUC 0.80 versus 0.64; p < 0.001). Age, sex, and APOE ɛ4 carrier status did not the diagnostic performance of plasma Aβ42/Aβ40 to predict amyloid PET positivity in A4 Study participants. Conclusion: Plasma Aβ42/Aβ40 may serve as a potential biomarker for predicting elevated amyloid in the brain. Utilizing blood testing over PET imaging may improve screening efficiency into clinical trials.

Publisher

IOS Press

Subject

Psychiatry and Mental health,Geriatrics and Gerontology,Clinical Psychology,General Medicine,General Neuroscience

Cited by 7 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3