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中国痴呆人群中脑脊液核心阿尔茨海默病生物标志物与β-淀粉样蛋白 PET 的相关性。

Correlation between Cerebrospinal Fluid Core Alzheimer's Disease Biomarkers and β-Amyloid PET in Chinese Dementia Population.

机构信息

Department of Nuclear Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.

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 230001, China.

出版信息

ACS Chem Neurosci. 2022 May 18;13(10):1558-1565. doi: 10.1021/acschemneuro.2c00120. Epub 2022 Apr 27.

Abstract

The current diagnoses of Alzheimer's disease (AD) mainly rely on such measures as amyloid-β (Aβ) and tau neuropathology biomarkers in vivo via cerebrospinal fluid (CSF) and positron emission tomography (PET) imaging, which had been systematically studied in Caucasian individuals, whereas diagnostic performances of these approaches in Chinese dementia population still remain unclear. This study investigated the associations between the levels of CSF core AD biomarkers, including phosphorylated tau (p-Tau181), total tau (t-Tau), Aβ42, and Aβ40 measured by the single-molecule array (Simoa) and cerebral Aβ deposition status assessed by F-Florbetapir PET (Aβ PET), and evaluated the predictive values of CSF core AD biomarkers in discriminating Aβ PET status in a clinical dementia cohort of the Chinese population, which consisted of patients with mild cognitive impairment (MCI), AD dementia, and non-Alzheimer's dementia disease (Non-ADD). Global standard uptake value ratios (SUVRs) were calculated by Aβ PET, which was divided into positive (Aβ+) and negative (Aβ-) through visual analysis. CSF p-Tau181 and p-Tau181/t-Tau ratio were positively correlated with the global SUVR, while CSF Aβ42 and Aβ42/Aβ40 ratio were negatively correlated with the global SUVR. CSF Aβ40 has the highest predictive value in discriminating the MCI group from the AD group, while CSF p-Tau181 was applied to discriminate the AD group from the non-ADD group. CSF Aβ42/Aβ40 ratio, as the optimal predictive factor, was combined with APOE ε4 status rather than age and education, which could improve the predictive ability in differentiating the Aβ+ group from the Aβ- group. The results reveal the universal applicability of CSF core AD biomarkers and Aβ PET imaging in Chinese dementia population, which is helpful in clinical practice and drug trials in China.

摘要

目前阿尔茨海默病(AD)的诊断主要依赖于通过脑脊液(CSF)和正电子发射断层扫描(PET)成像进行体内淀粉样蛋白-β(Aβ)和tau 神经病理学生物标志物等措施,这些措施已经在白种人群体中进行了系统研究,而这些方法在中国痴呆人群中的诊断性能仍不清楚。本研究调查了 CSF 核心 AD 生物标志物水平与 Aβ PET 之间的相关性,这些生物标志物包括通过单分子阵列(Simoa)测量的磷酸化 tau(p-Tau181)、总 tau(t-Tau)、Aβ42 和 Aβ40,以及通过 F-Florbetapir PET(Aβ PET)评估的脑内 Aβ 沉积状态,并评估了 CSF 核心 AD 生物标志物在区分中国人群临床痴呆队列中 Aβ PET 状态的预测价值,该队列包括轻度认知障碍(MCI)、AD 痴呆和非阿尔茨海默病痴呆(Non-ADD)患者。通过 Aβ PET 计算了全局标准摄取比值(SUVR),通过视觉分析将其分为阳性(Aβ+)和阴性(Aβ-)。CSF p-Tau181 和 p-Tau181/t-Tau 比值与全球 SUVR 呈正相关,而 CSF Aβ42 和 Aβ42/Aβ40 比值与全球 SUVR 呈负相关。CSF Aβ40 对区分 MCI 组和 AD 组具有最高的预测价值,而 CSF p-Tau181 则用于区分 AD 组和非 ADD 组。CSF Aβ42/Aβ40 比值作为最佳预测因素,与 APOE ε4 状态结合使用,而不是年龄和教育程度,这可以提高区分 Aβ+组和 Aβ-组的预测能力。结果表明 CSF 核心 AD 生物标志物和 Aβ PET 成像在中国人群中的普遍适用性,这有助于在中国的临床实践和药物试验中使用。

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