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Journal Article Ppublish 2 citations

PubMed: 39887504 DOI: 10.1002/alz.14536

Plasma p-tau217 and p-tau217/Aβ1-42 are effective biomarkers for identifying CSF- and PET imaging-diagnosed Alzheimer's disease: Insights for research and clinical practice.

Alzheimers Dement 21(2):e14536

Authors: Xiaomei Zhong, Qiang Wang, Mingfeng Yang, Gaohong Lin, Kexin Yao, Zhangying Wu, Danyan Xu, Huarong Zhou, Ben Chen, Haishan Shi, Min Zhang, Xiaolei Shi, Yijie Zeng, Jingyi Lao, Shuang Liang, JiaFu Li, Qin Liu, Huanmin Liu, Yunheng Chen, Yicheng Lin, Cong Ouyang, Jieqin Lv, Xiang Liang, Yuwang Cheng, Pengcheng Ran, Baoying Gong, Bin Zhang, Jianwen Guo, Hong Zhang, Sen Liu, Jihui Zhang, Haiying Liu, Yuping Ning

Affiliations

  • The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, China.
  • Departments of Nuclear Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Secondary Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China.
  • Pason Neuroscience Research Center, Beijing, China.
  • Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, China.

Abstract

INTRODUCTION

With the advancement of disease-modifying therapies for Alzheimer's disease (AD), validating plasma biomarkers against cerebrospinal fluid (CSF) and positron emission tomography (PET) standards is crucial in both research and real-world settings.

METHODS

We measured plasma phosphorylated tau (p-tau)217, p-tau181, amyloid beta (Aβ)1-40, Aβ1-42, and neurofilament light chain in research and real-world cohorts. Participants were categorized by brain amyloid status using US Food and Drug Administration/European Medicines Agency-approved CSF or PET methods.

RESULTS

Plasma p-tau217 and p-tau217/Aβ1-42 demonstrated superior accuracy in detecting brain amyloid pathologies, with area under the curve from 0.94 to 0.97 in all cohorts. Specificity was lower in the real-world cohort but improved significantly by integrating demographic and clinical factors, aligning performance with research cohorts. Additionally, plasma biomarkers exhibited strong correlations with their CSF counterparts and PET standardized uptake value ratios, with significant associations in amyloid-positive participants.

DISCUSSION

Plasma p-tau217 and p-tau217/Aβ1-42 are effective diagnostic tools. However, patient demographics, apolipoprotein E ε4 status, and cognitive condition must be considered to improve specificity in the clinical practice.

HIGHLIGHTS

Plasma phosphorylated tau (p-tau)217 and p-tau217/amyloid beta (Aβ)1-42 demonstrated exceptional accuracy (area under the curve: 0.94-0.97) in detecting brain amyloid pathologies across both research (Southern China Aging Brain Initiative [SCABI]-1, SCABI-2) and real-world clinical practice (RCP) cohorts. Incorporating patient-specific factors (sex, age, apolipoprotein E ε4, cognitive status) improved diagnostic specificity in the clinical RCP cohort, aligning its performance with that of research cohorts. Plasma biomarkers, particularly p-tau217 and their ratios, showed robust correlations with cerebrospinal fluid biomarkers and positron emission tomography amyloid standardized uptake value ratios, underscoring their value as non-invasive diagnostic alternatives. Plasma p-tau217 and p-tau217/Aβ1-42 proved highly effective in diagnosing amyloid burden, offering a practical solution to bridge research advancements with real-world clinical practice.

MeSH

Dementia, Alzheimer Disease, Tomography, Positron-Emission Tomography, Brain, Pathology, Cognitive Dysfunction, Biomarkers, Research, Amyloid, Apolipoproteins, Demography, Plasma

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