Glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, can be measured in blood samples, and has been associated with Alzheimer’s disease (AD). However, plasma GFAP has not been investigated in cognitively normal older adults at risk of AD, based on brain amyloid-β (Aβ) load. Cross-sectional analyses were carried out for plasma GFAP and plasma Aβ1–42/Aβ1–40 ratio, a blood-based marker associated with brain Aβ load, in participants (65–90 years) categorised into low (Aβ−, n = 63) and high (Aβ+, n = 33) brain Aβ load groups via Aβ positron emission tomography. Plasma GFAP, Aβ1–42, and Aβ1–40 were measured using the Single molecule array (Simoa) platform. Plasma GFAP levels were significantly higher (p < 0.00001), and plasma Aβ1–42/Aβ1–40 ratios were significantly lower (p < 0.005), in Aβ+ participants compared to Aβ− participants, adjusted for covariates age, sex, and apolipoprotein E-ε4 carriage. A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished Aβ+ from Aβ− (area under the curve, AUC = 0.78), but was outperformed when plasma GFAP was added to the base model (AUC = 0.91) and further improved with plasma Aβ1–42/Aβ1–40 ratio (AUC = 0.92). The current findings demonstrate that plasma GFAP levels are elevated in cognitively normal older adults at risk of AD. These observations suggest that astrocytic damage or activation begins from the pre-symptomatic stage of AD and is associated with brain Aβ load. Observations from the present study highlight the potential of plasma GFAP to contribute to a diagnostic blood biomarker panel (along with plasma Aβ1–42/Aβ1–40 ratios) for cognitively normal older adults at risk of AD.

胶质纤维酸性蛋白（GFAP）是一种星形细胞骨架蛋白，可以在血液样本中进行测定，并且与阿尔茨海默氏病（AD）有关。然而，基于脑淀粉样蛋白-β（Aβ）负荷，尚未对具有认知风险的认知正常的成年人进行血浆GFAP的研究。对参加者（65-90岁）分类为低（Aβ-，n  = 63 ）的血浆GFAP和血浆Aβ1-42/Aβ1-4比率（与脑Aβ负荷相关的基于血液的标志物）进行了横断面分析）和高（Aβ+，n  = 33）脑Aβ负荷组（通过Aβ正电子发射断层扫描）。使用单分子阵列（Simoa）平台测量血浆GFAP，Aβ1–42和Aβ1–40。血浆GFAP水平明显升高（p <0.00001），血浆Aβ1-42/Aβ1-4的比率显着降低（p <0.005），与Aβ-参与者相比，Aβ+参与者的年龄，性别和载脂蛋白E-ε4转运的协变量进行了调整。基于相同协变量的逻辑回归的接收器工作特性曲线，基本模型，将Aβ+与Aβ-区别开（曲线下面积，AUC = 0.78），但是当将血浆GFAP添加到基本模型中时，该性能优于= 0.91），并随着血浆Aβ1-42/Aβ1-4比率（AUC = 0.92）进一步改善。目前的发现表明，患有AD风险的认知正常的成年人血浆GFAP水平升高。这些观察结果表明，星形胶质细胞的损伤或激活从AD的症状前阶段开始，并与脑Aβ负荷有关。