血浆生物标志物可在无痴呆的基于人群的队列中识别脑淀粉样蛋白、tau蛋白和神经退行性变异常。

Plasma biomarkers identify brain ATN abnormalities in a dementia-free population-based cohort.

作者信息

Dresse Menayit Tamrat, Ferreira Pamela C L, Prasadan Akshay, Diaz Jihui L, Zeng Xuemei, Bellaver Bruna, Povala Guilherme, Villemagne Victor L, Kamboh M Ilyas, Cohen Ann D, Pascoal Tharick A, Ganguli Mary, Snitz Beth E, Shaaban C Elizabeth, Karikari Thomas K

机构信息

Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Department of Psychiatry, School of Medicine, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15213, USA.

出版信息

medRxiv. 2025 Apr 28:2025.04.27.25326360. doi: 10.1101/2025.04.27.25326360.

DOI:10.1101/2025.04.27.25326360

PMID:40343022

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12060967/

Abstract

INTRODUCTION

Using the ATN framework, we evaluated the potential of plasma biomarkers to identify abnormal brain amyloid-beta (Aβ) positron emission tomography (PET), tau-PET and neurodegeneration in a socioeconomically disadvantaged population-based cohort.

METHODS

Community-dwelling dementia-free (n=113, including 102 (91%) cognitively normal) participants underwent ATN neuroimaging and plasma biomarker assessments.

RESULTS

Plasma Aβ42/Aβ40, p-tau181, and p-tau217 showed significant associations with Aβ-PET status (adjusted odds ratio [AOR] of 1.7410, 1.47, and 3.4310 respectively [p-values<0.05]), with p-tau217 demonstrating the highest classification accuracy for Aβ-PET status (AUC=0.94). Plasma p-tau181 and p-tau217 showed significant associations with tau-PET status (AOR: 1.50 and 22.24, respectively, p-values<0.05), with comparable classification accuracies for tau-PET status (AUC=0.74 and 0.70, respectively). Only plasma NfL showed significant association with neurodegeneration based on cortical thickness (AOR=1.09, p-value<0.05).

CONCLUSION

Our findings highlight potential of plasma p-tau217 as a biomarker for brain Aβ and tau pathophysiology, p-tau181 for tau abnormalities, and NfL for neurodegeneration in the community.

摘要

引言

我们使用ATN框架，在一个社会经济条件不利的人群队列中，评估了血浆生物标志物识别异常脑淀粉样β（Aβ）正电子发射断层扫描（PET）、tau-PET和神经退行性变的潜力。

方法

居住在社区的无痴呆参与者（n = 113，包括102名（91%）认知正常者）接受了ATN神经影像学检查和血浆生物标志物评估。

结果

血浆Aβ42/Aβ40、p-tau181和p-tau217与Aβ-PET状态显著相关（调整优势比[AOR]分别为1.74×10、1.47和3.43×10 [p值<0.05]），其中p-tau217对Aβ-PET状态的分类准确率最高（AUC = 0.94）。血浆p-tau181和p-tau217与tau-PET状态显著相关（AOR分别为1.50和22.24，p值<0.05），对tau-PET状态的分类准确率相当（AUC分别为0.74和0.70）。仅血浆神经丝轻链（NfL）基于皮质厚度与神经退行性变显著相关（AOR = 1.09，p值<0.05）。