机器学习揭示的AD生物标志物组合模型可精确预测阿尔茨海默病痴呆：中国衰老与神经退行性疾病倡议（CANDI）研究

A combination model of AD biomarkers revealed by machine learning precisely predicts Alzheimer's dementia: China Aging and Neurodegenerative Initiative (CANDI) study.

作者信息

Gao Feng, Lv Xinyi, Dai Linbin, Wang Qiong, Wang Peng, Cheng Zhaozhao, Xie Qiang, Ni Ming, Wu Yan, Chai Xianliang, Wang Wenjing, Li Huaiyu, Yu Feng, Cao Yuqin, Tang Fang, Pan Bo, Wang Guoping, Deng Kexue, Wang Shicun, Tang Qiqiang, Shi Jiong, Shen Yong

机构信息

Department of Neurology, Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China.

Neurodegenerative Disorder Research Center, Anhui Province Key Laboratory of Biomedical Aging Research, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China.

出版信息

Alzheimers Dement. 2023 Mar;19(3):749-760. doi: 10.1002/alz.12700. Epub 2022 Jun 6.

DOI:10.1002/alz.12700

PMID:35668045

Abstract

INTRODUCTION

To test the utility of the "A/T/N" system in the Chinese population, we study core Alzheimer's disease (AD) biomarkers in a newly established Chinese cohort.

METHODS

A total of 411 participants were selected, including 96 cognitively normal individuals, 94 patients with mild cognitive impairment (MCI) patients, 173 patients with AD, and 48 patients with non-AD dementia. Fluid biomarkers were measured with single molecule array. Amyloid beta (Aβ) deposition was determined by F-Flobetapir positron emission tomography (PET), and brain atrophy was quantified using magnetic resonance imaging (MRI).

RESULTS

Aβ42/Aβ40 was decreased, whereas levels of phosphorylated tau (p-tau) were increased in cerebrospinal fluid (CSF) and plasma from patients with AD. CSF Aβ42/Aβ40, CSF p-tau, and plasma p-tau showed a high concordance in discriminating between AD and non-AD dementia or elderly controls. A combination of plasma p-tau, apolipoprotein E (APOE) genotype, and MRI measures accurately predicted amyloid PET status.

DISCUSSION

These results revealed a universal applicability of the "A/T/N" framework in a Chinese population and established an optimal diagnostic model consisting of cost-effective and non-invasive approaches for diagnosing AD.

摘要

引言

为了测试“A/T/N”系统在中国人群中的实用性，我们在一个新建立的中国队列中研究了核心阿尔茨海默病（AD）生物标志物。

方法

共选取411名参与者，包括96名认知正常个体、94名轻度认知障碍（MCI）患者、173名AD患者和48名非AD痴呆患者。使用单分子阵列测量体液生物标志物。通过氟代贝他匹正电子发射断层扫描（PET）测定淀粉样β蛋白（Aβ）沉积，并使用磁共振成像（MRI）对脑萎缩进行量化。

结果

AD患者脑脊液（CSF）和血浆中的Aβ42/Aβ40降低，而磷酸化tau蛋白（p-tau）水平升高。CSF Aβ42/Aβ40、CSF p-tau和血浆p-tau在区分AD与非AD痴呆或老年对照方面具有高度一致性。血浆p-tau、载脂蛋白E（APOE）基因型和MRI测量的组合准确预测了淀粉样PET状态。