在认知功能正常的老年人中，比较 APOE4 相关阿尔茨海默病风险水平为三级的患者血浆 p-tau181、p-tau231 和神经胶质纤维酸性蛋白。

Head-to-head comparison of plasma p-tau181, p-tau231 and glial fibrillary acidic protein in clinically unimpaired elderly with three levels of APOE4-related risk for Alzheimer's disease.

机构信息

Turku PET Centre, University of Turku, Turku University Hospital, Turku, Finland; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Turku PET Centre, University of Turku, Turku University Hospital, Turku, Finland.

出版信息

Neurobiol Dis. 2023 Jul;183:106175. doi: 10.1016/j.nbd.2023.106175. Epub 2023 Jun 1.

DOI:10.1016/j.nbd.2023.106175

PMID:37268240

Abstract

Plasma phosphorylated tau (p-tau) and glial fibrillary acidic protein (GFAP) both reflect early changes in Alzheimer's disease (AD) pathology. Here, we compared the biomarker levels and their association with regional β-amyloid (Aβ) pathology and cognitive performance head-to-head in clinically unimpaired elderly (n = 88) at three levels of APOE4-related genetic risk for sporadic AD (APOE4/4 n = 19, APOE3/4 n = 32 or non-carriers n = 37). Concentrations of plasma p-tau181, p-tau231 and GFAP were measured using Single molecule array (Simoa), regional Aβ deposition with C-PiB positron emission tomography (PET), and cognitive performance with a preclinical composite. Significant differences in plasma p-tau181 and p-tau231, but not plasma GFAP concentrations were present between the APOE4 gene doses, explained solely by brain Aβ load. All plasma biomarkers correlated positively with Aβ PET in the total study population. This correlation was driven by APOE3/3 carriers for plasma p-tau markers and APOE4/4 carriers for plasma GFAP. Voxel-wise associations with amyloid-PET revealed different spatial patterns for plasma p-tau markers and plasma GFAP. Only higher plasma GFAP correlated with lower cognitive scores. Our observations suggest that plasma p-tau and plasma GFAP are both early AD markers reflecting different Aβ-related processes.

摘要

血浆磷酸化 tau（p-tau）和神经胶质纤维酸性蛋白（GFAP）均可反映阿尔茨海默病（AD）病理的早期变化。在这里，我们在三个与散发性 AD 的 APOE4 相关遗传风险水平（APOE4/4 n=19、APOE3/4 n=32 或非携带者 n=37）的认知正常的老年人（n=88）中比较了生物标志物水平及其与区域性β-淀粉样蛋白（Aβ）病理和认知表现的关联。使用单分子阵列（Simoa）测量了血浆 p-tau181、p-tau231 和 GFAP 的浓度，使用 C-PiB 正电子发射断层扫描（PET）测量了区域性 Aβ 沉积，并用临床前综合指标测量了认知表现。APOE4 基因剂量之间存在血浆 p-tau181 和 p-tau231 浓度的显著差异，但 GFAP 浓度无差异，仅能通过脑 Aβ 负荷来解释。所有血浆生物标志物与总研究人群的 Aβ PET 均呈正相关。这种相关性是由血浆 p-tau 标志物的 APOE3/3 携带者和血浆 GFAP 的 APOE4/4 携带者驱动的。与淀粉样蛋白-PET 的体素相关性显示出血浆 p-tau 标志物和血浆 GFAP 之间不同的空间模式。只有较高的血浆 GFAP 与较低的认知评分相关。我们的观察结果表明，血浆 p-tau 和血浆 GFAP 均为早期 AD 标志物，反映了不同的与 Aβ 相关的过程。