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Journal Article Ppublish 3 citations

PubMed: 39907189 DOI: 10.1002/alz.14526

Differential roles of Alzheimer's disease plasma biomarkers in stepwise biomarker-guided diagnostics.

Alzheimers Dement 21(2):e14526

Authors: Hyemin Jang, Daeun Shin, Heejin Yoo, Henrik Zetterberg, Kaj Blennow, Fernando Gonzalez-Ortiz, Nicholas J Ashton, Theresa A Day, Eun Hye Lee, Jihwan Yun, Duk L Na, Hee Jin Kim, Sung Hoon Kang, Ko Woon Kim, Si Eun Kim, Yeo Jin Kim, Yeshin Kim, Jaeho Kim, Chi-Hun Kim, Min Young Chun, Na Yeon Jung, Soo Hyun Cho, Jun Pyo Kim, Sang Won Seo

Affiliations

  • Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
  • Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.
  • Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Göteborg, Sweden.
  • Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
  • UK Dementia Research Institute at UCL, London, UK.
  • Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, P.R. China.
  • Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
  • Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
  • Neurodegenerative 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.
  • King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, De Crespigny Park, London, UK.
  • NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, De Crespigny Park, London, UK.
  • Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
  • Lilly Corporate Center, Eli Lilly and Company, Indianapolis, Indiana, USA.
  • Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon-si, Gyeonggi-do, Republic of Korea.
  • Alzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea.
  • Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
  • Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea.
  • Department of Neurology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
  • Department of Neurology, Jeonbuk National University Medical School and Hospital, Jeonju-si, Republic of Korea.
  • Department of Neurology, Inje University College of Medicine, Haeundae Paik Hospital, Busan, Republic of Korea.
  • Department of Neurology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea.
  • Department of Neurology, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do, Republic of Korea.
  • Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea.
  • Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si, Gyeonggi-do, Republic of Korea.
  • Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Department of Neurology, Yongin Severance Hospital, Yonsei University Health System, Yongin-si, Gyeonggi-do, Republic of Korea.
  • Department of Neurology, Pusan National University Yangsan Hospital, Research Institute for Convergence of Biomedical Science and Technology, Yangsan-si, Gyeongsangnam-do, Republic of Korea.
  • Department of Neurology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Republic of Korea.

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.

MeSH

Dementia, Alzheimer Disease, Positron-Emission Tomography, Pathology, Cognitive Dysfunction, Biomarkers, Prognosis, Plasma

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