Shan Guogen, Li Hui, Zhang Yahui, Wang Guoqiao, Bernick Charles
Department of Biostatistics, University of Florida, Gainesville, FL, United States.
School of Smart Health, Chongqing Polytechnic University of Electronic Technology, Chongqing, China.
Front Aging Neurosci. 2025 May 9;17:1576373. doi: 10.3389/fnagi.2025.1576373. eCollection 2025.
Blood biomarkers for Alzheimer's disease (AD) can be utilized as surrogate endpoints to accelerate therapeutic development for this condition.
We assessed the association between short-term changes in blood biomarkers and long-term declines in cognitive and brain structure volume measures using the ADNI database, with a focus on amyloid- (A)-positive participants. In our statistical models, the association was calculated after controlling for age, sex, and other possible confounding covariates. Additionally, outliers were removed before running the statistical models to ensure that the results were robust.
A trend association was found between changes in the levels of plasma neurofilament light (NfL) at 12 months and changes in the scores on the Mini-Mental State Examination (MMSE) at 24 months in Aβ-positive mild cognitive impairment (MCI) patients. For Apositive dementia patients, a trend association was observed between changes in plasma p-tau181 levels and changes in whole brain and middle temporal volume.
Increased plasma levels of NfL or p-tau181 blood biomarkers were found to be associated with reduced brain volumes and/or declined cognitive outcomes, suggesting that these blood biomarkers may have a predictive role in AD trials.
阿尔茨海默病（AD）的血液生物标志物可用作替代终点，以加速针对该病症的治疗开发。
我们使用阿尔茨海默病神经影像学倡议（ADNI）数据库评估了血液生物标志物的短期变化与认知及脑结构体积测量的长期下降之间的关联，重点关注淀粉样蛋白（A）阳性参与者。在我们的统计模型中，在控制年龄、性别和其他可能的混杂协变量后计算关联。此外，在运行统计模型之前去除异常值，以确保结果的稳健性。
在Aβ阳性轻度认知障碍（MCI）患者中，发现12个月时血浆神经丝轻链（NfL）水平的变化与24个月时简易精神状态检查表（MMSE）评分的变化之间存在趋势关联。对于A阳性痴呆患者，观察到血浆p-tau181水平的变化与全脑和颞中回体积的变化之间存在趋势关联。
发现血浆NfL或p-tau181血液生物标志物水平升高与脑容量减少和/或认知结果下降有关，表明这些血液生物标志物可能在AD试验中具有预测作用。
