Department of Biomedical Sciences, Macquarie University, North Ryde, New South Wales, Australia.
School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
Alzheimers Dement. 2022 Jun;18(6):1141-1154. doi: 10.1002/alz.12447. Epub 2021 Sep 8.
This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t-tau), phosphorylated tau (p-tau181 and p-tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD).
Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ-) or presence (Aβ+) of brain amyloidosis.
Plasma GFAP, t-tau, p-tau181, and p-tau231 concentrations were higher in Aβ+ CU compared with Aβ- CU cross-sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aβ+ and Aβ- CU; however, no statistically significant differences were observed between the AUCs of GFAP, p-tau181, and p-tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t-tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene (APOE) ε4 status with GFAP was observed to have a higher AUC (>90%) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p-tau181 in Aβ+ CU and increased NFL in Aβ- CU, over a 12-month duration. GFAP, p-tau181, p-tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippocampal volume.
These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p-tau for preclinical AD.
本研究平行比较了血浆神经胶质纤维酸性蛋白（GFAP）、总 tau（t-tau）、磷酸化 tau（p-tau181 和 p-tau231）和神经丝轻链（NFL）在临床前阿尔茨海默病（AD）中的诊断和纵向监测潜力。
使用 Simoa 测定法在认知正常的老年人（CU）中测量血浆蛋白，这些老年人要么存在（Aβ+）要么不存在（Aβ-）脑淀粉样蛋白。
Aβ+ CU 与 Aβ- CU 相比，血浆 GFAP、t-tau、p-tau181 和 p-tau231 浓度更高。GFAP 在区分 Aβ+和 Aβ- CU 方面具有最大的效应量和曲线下面积（AUC）；然而，GFAP、p-tau181 和 p-tau231 的 AUC 之间没有统计学上的显著差异，但均显著高于 NFL 的 AUC，且 GFAP 的 AUC 高于 t-tau 的 AUC。与包括 AD 风险因素、年龄、性别和载脂蛋白 E 基因（APOE）ε4 状态的基础模型（BM）组合相比，观察到包含 GFAP 的组合具有更高的 AUC（>90%）（BM）与当前研究中调查的任何其他蛋白质的组合。纵向分析显示，在 12 个月的时间内，Aβ+ CU 中 GFAP 和 p-tau181 增加，Aβ- CU 中 NFL 增加。GFAP、p-tau181、p-tau231 和 NFL 与认知显著相关，而与海马体积无显著相关性。
这些发现强调了 GFAP 和 p-tau 在临床前 AD 中的诊断和纵向监测潜力。
