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Alzheimers. Dement., Feb 05 2025, | https://doi.org/10.1002/alz.14526
Differential roles of Alzheimer's disease plasma biomarkers in stepwise biomarker-guided diagnostics
Hyemin Jang 1, Daeun Shin 2, Heejin Yoo 2, Henrik Zetterberg 3,4,5,6,7,8, Kaj Blennow 3,4,9,10, Fernando Gonzalez-Ortiz 3,4, Nicholas J Ashton 3,11,12,13, Theresa A Day 14, Eun Hye Lee 2, Jihwan Yun 15, Duk L Na 2, Hee Jin Kim 2,16,17,18, Sung Hoon Kang 19, Ko Woon Kim 20, Si Eun Kim 21, Yeo Jin Kim 22, Yeshin Kim 23, Jaeho Kim 24, Chi-Hun Kim 25, Min Young Chun 26,27, Na Yeon Jung 28, Soo Hyun Cho 29, Jun Pyo Kim 2, Sang Won Seo 2,16,17,18; K‐ROAD study groups
1Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
2Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
3Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.
4Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Göteborg, Sweden.
5Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
6UK Dementia Research Institute at UCL, London, UK.
7Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, P.R. China.
8Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
9Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
10Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, P.R. China.
11King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, De Crespigny Park, London, UK.
12NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, De Crespigny Park, London, UK.
13Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
14Lilly Corporate Center, Eli Lilly and Company, Indianapolis, Indiana, USA.
15Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon-si, Gyeonggi-do, Republic of Korea.
16Alzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea.
17Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
18Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea.
19Department of Neurology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
20Department of Neurology, Jeonbuk National University Medical School and Hospital, Jeonju-si, Republic of Korea.
21Department of Neurology, Inje University College of Medicine, Haeundae Paik Hospital, Busan, Republic of Korea.
22Department of Neurology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea.
23Department of Neurology, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do, Republic of Korea.
24Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea.
25Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si, Gyeonggi-do, Republic of Korea.
26Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea.
27Department of Neurology, Yongin Severance Hospital, Yonsei University Health System, Yongin-si, Gyeonggi-do, Republic of Korea.
28Department of Neurology, Pusan National University Yangsan Hospital, Research Institute for Convergence of Biomedical Science and Technology, Yangsan-si, Gyeongsangnam-do, Republic of Korea.
29Department of Neurology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Republic of Korea.
Hyemin Jang and Daeun Shin contributed equally to this article as co-first authors.
Jun Pyo Kim and Sang Won Seo contributed equally to this article as co-corresponding authors.
Corresponding Authors: Jun Pyo Kim, Sang Won Seo
1Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
2Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
3Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.
4Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Göteborg, Sweden.
5Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
6UK Dementia Research Institute at UCL, London, UK.
7Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, P.R. China.
8Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
9Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
10Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, P.R. China.
11King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, De Crespigny Park, London, UK.
12NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, De Crespigny Park, London, UK.
13Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
14Lilly Corporate Center, Eli Lilly and Company, Indianapolis, Indiana, USA.
15Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon-si, Gyeonggi-do, Republic of Korea.
16Alzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea.
17Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
18Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea.
19Department of Neurology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
20Department of Neurology, Jeonbuk National University Medical School and Hospital, Jeonju-si, Republic of Korea.
21Department of Neurology, Inje University College of Medicine, Haeundae Paik Hospital, Busan, Republic of Korea.
22Department of Neurology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea.
23Department of Neurology, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do, Republic of Korea.
24Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea.
25Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si, Gyeonggi-do, Republic of Korea.
26Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea.
27Department of Neurology, Yongin Severance Hospital, Yonsei University Health System, Yongin-si, Gyeonggi-do, Republic of Korea.
28Department of Neurology, Pusan National University Yangsan Hospital, Research Institute for Convergence of Biomedical Science and Technology, Yangsan-si, Gyeongsangnam-do, Republic of Korea.
29Department of Neurology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Republic of Korea.
Hyemin Jang and Daeun Shin contributed equally to this article as co-first authors.
Jun Pyo Kim and Sang Won Seo contributed equally to this article as co-corresponding authors.
Corresponding Authors: Jun Pyo Kim, Sang Won Seo
Abstract
Introduction: This study aimed to investigate the differential roles of various plasma biomarkers in a stepwise diagnostic strategy for Alzheimer's disease (AD).
Methods: A total of 2984 participants, including 666 cognitively unimpaired (CU), 2032 with Alzheimer's clinical syndrome (ACS), and 286 non-ACS individuals, were recruited. Plasma amyloid beta (Aβ) 42/40, four phosphorylated tau (p-tau) epitopes, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels were measured using immunoassays.
Results: NfL demonstrated fair to excellent accuracy in differentiating non-ACS from CU groups (area under the curve [AUC], 0.79 to 0.94). p-tau217 had the highest accuracy for identifying Aβ (AUC 0.94) and tau positron emission tomography status (AUC 0.91). In the ACS group, p-tau217 was the strongest predictor of cognitive decline (p < .001).
Discussion: NfL may serve as a useful screening tool, while p-tau217 is particularly valuable for confirming AD pathology and prognosis.
Highlights: Plasma NfL could screen for cognitive impairment. p-tau217 reliably detects AD pathology, regardless of diagnosis. p-tau217 and GFAP predict prognosis in ACS. Each plasma biomarker plays a distinct role in stepwise AD diagnostics.
Methods: A total of 2984 participants, including 666 cognitively unimpaired (CU), 2032 with Alzheimer's clinical syndrome (ACS), and 286 non-ACS individuals, were recruited. Plasma amyloid beta (Aβ) 42/40, four phosphorylated tau (p-tau) epitopes, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels were measured using immunoassays.
Results: NfL demonstrated fair to excellent accuracy in differentiating non-ACS from CU groups (area under the curve [AUC], 0.79 to 0.94). p-tau217 had the highest accuracy for identifying Aβ (AUC 0.94) and tau positron emission tomography status (AUC 0.91). In the ACS group, p-tau217 was the strongest predictor of cognitive decline (p < .001).
Discussion: NfL may serve as a useful screening tool, while p-tau217 is particularly valuable for confirming AD pathology and prognosis.
Highlights: Plasma NfL could screen for cognitive impairment. p-tau217 reliably detects AD pathology, regardless of diagnosis. p-tau217 and GFAP predict prognosis in ACS. Each plasma biomarker plays a distinct role in stepwise AD diagnostics.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-06)
- 국내(교신)+국외 연구진
- 의약학 > 응용의학
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