Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.
Institute of Brain Science and Brain-inspired Research, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, P.R. China.
J Alzheimers Dis. 2023;96(2):845-858. doi: 10.3233/JAD-230932.
Plasma biomarkers have emerged as a promising approach for characterizing pathophysiology in mild cognitive impairment (MCI) and Alzheimer's disease (AD).
We aimed to characterize plasma biomarkers for AD and neurodegeneration across the AD clinical continuum, and to assess their ability to differentiate between AD, MCI, and normal cognition.
This population-based study engaged 1,446 rural-dwelling older adults (age ≥60 years, 61.0% women) derived from MIND-China; of these, 402 were defined with MCI and 142 with AD. Plasma amyloid-β (Aβ), total tau (t-tau), and neurofilament light chain (NfL) concentrations were analyzed using the Simoa platform. Data were analyzed using linear and logistic regression models, and receiver operating characteristic (ROC) analysis.
Across the AD clinical spectrum, plasma Aβ40 and NfL increased, whereas Aβ42/Aβ40 ratio decreased. Plasma t-tau was higher in people with AD dementia than those with MCI or normal cognition. Plasma NfL outperformed other biomarkers in differentiating AD from normal cognition (area under the ROC curve [AUC] = 0.75), but all plasma biomarkers performed poorly to distinguish MCI from normal cognition (AUC <0.60). Plasma NfL in combination with age, sex, education, and APOE genotype yielded the AUC of 0.87 for differentiating between AD and normal cognition, 0.79 between AD and MCI, and 0.64 between MCI and normal cognition.
In this Chinese population, AD plasma biomarkers vary by age, sex, and APOE genotype. Plasma Aβ, t-tau, and NfL differ across the AD clinical spectrum, and plasma NfL appears to be superior to plasma Aβ and t-tau for defining the clinical spectrum.
血浆生物标志物已成为一种有前途的方法，可以用于描述轻度认知障碍（MCI）和阿尔茨海默病（AD）中的病理生理学。
我们旨在描述 AD 临床连续体中 AD 和神经退行性变的血浆生物标志物，并评估它们区分 AD、MCI 和正常认知的能力。
这项基于人群的研究涉及了来自 MIND-China 的 1446 名农村居住的老年人（年龄≥60 岁，61.0%为女性）；其中，402 人被定义为 MCI，142 人为 AD。使用 Simoa 平台分析血浆淀粉样蛋白-β（Aβ）、总 tau（t-tau）和神经丝轻链（NfL）浓度。使用线性和逻辑回归模型以及接收者操作特征（ROC）分析进行数据分析。
在 AD 临床谱中，血浆 Aβ40 和 NfL 增加，而 Aβ42/Aβ40 比值降低。与 MCI 或正常认知相比，AD 痴呆患者的血浆 t-tau 更高。与其他生物标志物相比，血浆 NfL 在区分 AD 与正常认知方面表现更好（ROC 曲线下面积[AUC] = 0.75），但所有血浆生物标志物在区分 MCI 与正常认知方面表现不佳（AUC <0.60）。将血浆 NfL 与年龄、性别、教育程度和 APOE 基因型相结合，可区分 AD 与正常认知的 AUC 为 0.87，区分 AD 与 MCI 的 AUC 为 0.79，区分 MCI 与正常认知的 AUC 为 0.64。
在这个中国人群中，AD 血浆生物标志物随年龄、性别和 APOE 基因型而变化。AD 临床谱中血浆 Aβ、t-tau 和 NfL 不同，血浆 NfL 似乎比血浆 Aβ和 t-tau 更适合定义临床谱。
