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Alzheimer's & dementia : the journal of the Alzheimer's Association
Published

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

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, K‐ROAD study groups

Abstract

Alzheimers Dement. 2025 Feb 5:e14526. doi: 10.1002/alz.14526. Online ahead of print.

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.

PMID:39907189 | DOI:10.1002/alz.14526

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg