Background:Measuring plasma glial fibrillary acidic protein (GFAP) alongside cortical amyloid-β (Aβ) may shed light on astrocytic changes in aging and Alzheimer’s disease (AD). Objective:To examine associations between plasma GFAP and cortical Aβ deposition in older adults across the typical aging-to-AD dementia spectrum. Methods:We studied two independent samples from UCSF (Cohort 1, N = 50; Cohort 2, N = 37) covering the spectra of clinical severity (CDR Sum of Boxes; CDR-SB) and Aβ-PET burden. Aβ-PET was completed with either florbetapir or Pittsburgh Compound B and standardized uptake value ratios were converted to the Centiloid (CL) scale for analyses. All participants with CDR-SB > 0 were Aβ-PET positive, while clinically normal participants (CDR-SB = 0) were a mix of Aβ-PET positive and negative. Regression analyses evaluated main effect and interaction associations between plasma GFAP, Aβ-PET, and clinical severity. Results:In both cohorts, plasma GFAP increased linearly with Aβ-PET CLs in clinically normal older adults. In Cohort 2, which included participants with more severe clinical dysfunction and Aβ-PET burden, the association between Aβ and GFAP became curvilinear (inverted U-shape; quadratic model R2 change = 0.165, p = 0.009), and Aβ-PET interacted with CDR-SB (R2 change = 0.164, p = 0.007): older adults with intermediate functional impairment (CDR-SB = 0.5–4.0) showed a weak (negative) association between Aβ-PET CLs and plasma GFAP, while older adults with dementia (CDR-SB > 4.0) showed a strong, negative association of higher Aβ-PET CLs with lower plasma GFAP. Conclusion:The relationship between astrocytic integrity and cortical Aβ may be highly dynamic, with linear, positive associations early in disease that diverge in more severe disease stages.

中文翻译：

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血浆神经胶质纤维酸性蛋白水平随淀粉样蛋白负荷和临床疾病阶段的光谱而不同

背景：测量血浆胶质纤维酸性蛋白 (GFAP) 和皮质淀粉样蛋白-β (Aβ) 可能有助于了解衰老和阿尔茨海默病 (AD) 中的星形胶质细胞变化。目的：在典型的衰老至 AD 痴呆谱系中检查老年人血浆 GFAP 与皮质 Aβ 沉积之间的关联。方法：我们研究了来自 UCSF 的两个独立样本（队列 1，N = 50；队列 2，N = 37），涵盖临床严重程度（CDR 框总和；CDR-SB）和 Aβ-PET 负荷谱。使用 florbetapir 或匹兹堡化合物 B 完成 Aβ-PET，并将标准化摄取值比率转换为 Centiloid (CL) 量表进行分析。所有 CDR-SB > 0 的参与者都是 Aβ-PET 阳性，而临床正常参与者 (CDR-SB = 0) 是 Aβ-PET 阳性和阴性的混合体。回归分析评估了血浆 GFAP、Aβ-PET 和临床严重程度之间的主要影响和相互作用关联。结果：在两个队列中，在临床正常的老年人中，血浆 GFAP 与 Aβ-PET CL 呈线性增加。在包括具有更严重临床功能障碍和 Aβ-PET 负担的参与者的队列 2 中，Aβ 和 GFAP 之间的关联变为曲线（倒 U 形；二次模型 R2 变化 = 0.165，p = 0.009），并且 Aβ-PET 与CDR-SB（R2 变化 = 0.164，p = 0.007）：中度功能障碍的老年人（CDR-SB = 0.5-4.0）显示 Aβ-PET CL 与血浆 GFAP 之间存在弱（负）相关性，而老年痴呆症患者(CDR-SB > 4.0) 显示出较高的 Aβ-PET CL 与较低的血浆 GFAP 呈强负相关。结论：