Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
Memory Clinic, Skåne University Hospital, Malmö, Sweden.
Alzheimers Res Ther. 2021 Mar 27;13(1):68. doi: 10.1186/s13195-021-00804-9.
Plasma glial fibrillary acidic protein (GFAP) is a marker of astroglial activation and astrocytosis. We assessed the ability of plasma GFAP to detect Alzheimer's disease (AD) pathology in the form of AD-related amyloid-β (Aβ) pathology and conversion to AD dementia in a mild cognitive impairment (MCI) cohort.
One hundred sixty MCI patients were followed for 4.7 years (average). AD pathology was defined using cerebrospinal fluid (CSF) Aβ42/40 and Aβ42/total tau (T-tau). Plasma GFAP was measured at baseline and follow-up using Simoa technology.
Baseline plasma GFAP could detect abnormal CSF Aβ42/40 and CSF Aβ42/T-tau with an AUC of 0.79 (95% CI 0.72-0.86) and 0.80 (95% CI 0.72-0.86), respectively. When also including APOE ε4 status as a predictor, the accuracy of the model to detect abnormal CSF Aβ42/40 status improved (AUC = 0.86, p = 0.02). Plasma GFAP predicted subsequent conversion to AD dementia with an AUC of 0.84 (95% CI 0.77-0.91), which was not significantly improved when adding APOE ε4 or age as predictors to the model. Longitudinal GFAP slopes for Aβ-positive and MCI who progressed to dementia (AD or other) were significantly steeper than those for Aβ-negative (p = 0.007) and stable MCI (p < 0.0001), respectively.
Plasma GFAP can detect AD pathology in patients with MCI and predict conversion to AD dementia.
血浆神经胶质纤维酸性蛋白（GFAP）是星形胶质细胞激活和星形胶质细胞增生的标志物。我们评估了血浆 GFAP 检测阿尔茨海默病（AD）病理学的能力，这种病理学表现为 AD 相关的淀粉样β（Aβ）病理学以及向轻度认知障碍（MCI）患者转化为 AD 痴呆。
160 名 MCI 患者接受了 4.7 年（平均）的随访。AD 病理学定义为使用脑脊液（CSF）Aβ42/40 和 Aβ42/总 tau（T-tau）。使用 Simoa 技术在基线和随访时测量血浆 GFAP。
基线血浆 GFAP 可以检测到异常 CSF Aβ42/40 和 CSF Aβ42/T-tau，AUC 分别为 0.79（95%CI 0.72-0.86）和 0.80（95%CI 0.72-0.86）。当将 APOE ε4 状态也作为预测因子时，该模型检测异常 CSF Aβ42/40 状态的准确性提高（AUC=0.86，p=0.02）。血浆 GFAP 预测随后转化为 AD 痴呆的 AUC 为 0.84（95%CI 0.77-0.91），当向模型中添加 APOE ε4 或年龄作为预测因子时，其并没有显著提高。Aβ 阳性和进展为痴呆（AD 或其他）的 MCI 患者的纵向 GFAP 斜率明显比 Aβ 阴性（p=0.007）和稳定的 MCI 患者更陡峭（p<0.0001）。
血浆 GFAP 可以检测 MCI 患者的 AD 病理学，并预测向 AD 痴呆的转化。
