배경: 혈액 바이오마커는 알츠하이머병(Alzheimer’s disease, AD)의 진단 및 예후에 대한 접근 방식을 크게 변화시켰으며, 여러 바이오마커를 조합하여 정확도가 향상되었다는 보고가 많이 나오고 있다. 이 논문에서는 여러 혈액 바이오마커를 활용한 QPLEX™ Alz plus assay kit (QM-Alz; Quantamatrix Inc., Korea)가 AD의 임상 진단에 도움이 될 수 있는지 살펴보고자 하였다. 또한, QM-Alz에 아포지단백 E 유전자형(ApoE)과 galectin-3 (Gal-3)을 추가했을 때 진단 정확도를 확인하였다.
방법: 임상적 진단을 통해 정상으로 분류된 48명과 AD로 분류된 80명을 대상으로 QM-Alz, ApoE, Gal-3 측정을 수행하였다. 임상적 AD 진단 결과 및 대뇌 아밀로이드 베타 침착 결과를 종속변수로 한 회귀분석 결과를 토대로 각 바이오마커 조합별 알고리즘을 도출하고, 각 바이오마커 조합의 곡선하면적(area under the curve, AUC), 민감도, 특이도를 계산하였다.
결과: 인지기능이 정상인 환자와 AD 환자를 구별하는 QM-Alz 알고리즘의 AUC는 0.758 (민감도 71.3%, 특이도 72.9%)이었다. QM-Alz에 ApoE 또는 Gal-3 결과를 추가하였을 때, 각각의 AUC 값은 0.804 (민감도 73.8%, 특이도 75.0%)와 0.842 (민감도 77.5%, 특이도 79.2%)로 향상되었다. 모든 바이오마커를 알고리즘에 통합했을 때 AUC는 0.860 (민감도 77.5%, 특이도 77.1%)이 되었다.
결론: QM-Alz는 AD의 임상 진단에 AUC 0.758의 정확도를 보여주었으며, 다양한 혈액 바이오마커를 조합함으로써 진단 정확도를 더욱 향상시킬 수 있었다.
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Original Article
다중 혈액 바이오마커를 활용한 알츠하이머병 임상 진단 정확도의 향상
Improvement of Clinical Diagnosis Accuracy of Alzheimer’s Disease Using Multiple Blood Biomarkers
서울대학교 전기정보공학부1, ㈜퀀타매트릭스2, 서울대학교 생명공학공동연구원3, 서울대학교 의학연구원 유전체의학연구소4, 치매극복연구개발사업단5, 성균관대학교 생명물리학과6
Hunjong Na, Ph.D.1,2, Ki Young Shin, Ph.D.3, Dokyung Lee, M.S.2, Changsik Yoon, M.S.2, Sun-Ho Han, M.D.4,5, Jong-Chan Park, M.D.4,5,6, Inhee Mook-Jung, M.D.4,5, Jisung Jang, Ph.D. 
2, Sunghoon Kwon, Ph.D. 1,2,3
2, Sunghoon Kwon, Ph.D. 1,2,3Department of Electrical and Computer Engineering1, Seoul National University, Seoul; QuantaMatrix Inc.2, Seoul; Bio-MAX Institute3, Seoul National University, Seoul; Genomic Medicine Institute4, Medical Research Center, Seoul National University, Seoul; Korea Dementia Research Center5, Seoul National University College of Medicine, Seoul; Department of Biophysics6, Sungkyunkwan University, Suwon, Korea
Correspondence to:Received: December 23, 2023; Revised: February 17, 2024; Accepted: March 11, 2024
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Lab Med Online 2024; 14(4): 330-338
Published October 1, 2024 https://doi.org/10.47429/lmo.2024.14.4.330
Copyright © The Korean Society for Laboratory Medicine.
Background: Blood biomarkers significantly change the diagnostic and prognostic approaches to Alzheimer’s disease (AD). There have also been many reports of enhanced accuracy achieved by combining multiple biomarkers. Our study aimed to assess the efficacy of the QPLEX™ Alz plus assay kit (QM-Alz; Quantamatrix Inc., Korea), which includes multiple blood biomarkers, in clinical AD diagnosis. After adding the apolipoprotein E genotype (ApoE) and galectin-3 (Gal-3) to QM-Alz, we tested whether the diagnostic accuracy increased.
Methods: A total of 128 clinically diagnosed participants were included. We identified the optimal algorithm combining QM-Alz, ApoE, and Gal-3 for diagnosing clinical AD dementia and cerebral amyloid-β deposition. The area under the curve (AUC), sensitivity (Sen), and specificity (Spe) of each biomarker combination were calculated.
Results: The AUC for the QM-Alz algorithm to differentiate between cognitively normal patients and patients with AD was 0.758 (Sen=71.3%, Spe=72.9%). When the QM-Alz algorithm was enriched with the addition of ApoE and Gal-3, their individual AUC values improved to 0.804 (Sen=73.8%, Spe=75.0%) and 0.842 (Sen=77.5%, Spe=79.2%), respectively. Furthermore, when all biomarkers were integrated into the algorithm, the resulting AUC was elevated to 0.860 (Sen=77.5%, Spe=77.1%).
Conclusions: The combination of various blood biomarkers, especially when integrating QM-Alz, ApoE, and Gal-3, significantly improves diagnostic accuracy for a more precise AD diagnosis.
Methods: A total of 128 clinically diagnosed participants were included. We identified the optimal algorithm combining QM-Alz, ApoE, and Gal-3 for diagnosing clinical AD dementia and cerebral amyloid-β deposition. The area under the curve (AUC), sensitivity (Sen), and specificity (Spe) of each biomarker combination were calculated.
Results: The AUC for the QM-Alz algorithm to differentiate between cognitively normal patients and patients with AD was 0.758 (Sen=71.3%, Spe=72.9%). When the QM-Alz algorithm was enriched with the addition of ApoE and Gal-3, their individual AUC values improved to 0.804 (Sen=73.8%, Spe=75.0%) and 0.842 (Sen=77.5%, Spe=79.2%), respectively. Furthermore, when all biomarkers were integrated into the algorithm, the resulting AUC was elevated to 0.860 (Sen=77.5%, Spe=77.1%).
Conclusions: The combination of various blood biomarkers, especially when integrating QM-Alz, ApoE, and Gal-3, significantly improves diagnostic accuracy for a more precise AD diagnosis.
Keywords
Alzheimer’s disease, Clinical diagnosis, Blood-based biomarker, Multiple biomarkers, QPLEX™
