Jang Hyemin, Shin Daeun, Yoo Heejin, Zetterberg Henrik, Blennow Kaj, Gonzalez-Ortiz Fernando, Ashton Nicholas J, Day Theresa A, Lee Eun Hye, Yun Jihwan, Na Duk L, Kim Hee Jin, Kang Sung Hoon, Kim Ko Woon, Kim Si Eun, Kim Yeo Jin, Kim Yeshin, Kim Jaeho, Kim Chi-Hun, Chun Min Young, Jung Na Yeon, Cho Soo Hyun, Kim Jun Pyo, Seo Sang Won
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.
Alzheimers Dement. 2025 Feb;21(2):e14526. doi: 10.1002/alz.14526. Epub 2025 Feb 5.
This study aimed to investigate the differential roles of various plasma biomarkers in a stepwise diagnostic strategy for Alzheimer's disease (AD).
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.
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).
NfL may serve as a useful screening tool, while p-tau217 is particularly valuable for confirming AD pathology and prognosis.
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.
本研究旨在探讨各种血浆生物标志物在阿尔茨海默病（AD）逐步诊断策略中的不同作用。
共招募了2984名参与者，包括666名认知未受损（CU）者、2032名患有阿尔茨海默病临床综合征（ACS）者和286名非ACS个体。使用免疫测定法测量血浆淀粉样蛋白β（Aβ）42/40、四种磷酸化tau（p-tau）表位、胶质纤维酸性蛋白（GFAP）和神经丝轻链（NfL）水平。
NfL在区分非ACS组和CU组方面表现出中等至优异的准确性（曲线下面积[AUC]，0.79至0.94）。p-tau217在识别Aβ（AUC 0.94）和tau正电子发射断层扫描状态（AUC 0.91）方面具有最高的准确性。在ACS组中，p-tau217是认知衰退最强的预测因子（p <.001）。
NfL可作为一种有用的筛查工具，而p-tau217对于确认AD病理和预后特别有价值。
血浆NfL可筛查认知障碍。无论诊断如何，p-tau217都能可靠地检测AD病理。p-tau217和GFAP可预测ACS的预后。每种血浆生物标志物在AD逐步诊断中都发挥着独特的作用。
