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

15 101

Cited 0 times in

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

MeSH: Aged ; Aged, 80 and over ; Alzheimer Disease* / blood ; Alzheimer Disease* / diagnosis ; Alzheimer Disease* / diagnostic imaging ; Amyloid beta-Peptides / blood ; Biomarkers* / blood ; Female ; Glial Fibrillary Acidic Protein / blood ; Humans ; Male ; Middle Aged ; Neurofilament Proteins* / blood ; Peptide Fragments / blood ; Positron-Emission Tomography ; tau Proteins* / blood

Keywords: Alzheimer's disease ; neurofilament light chain ; plasma biomarker ; positron emission tomography ; p‐tau217

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.