UK Dementia Research Institute, Department of Neurodegenerative Disease, University College London, London, UK.
Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
J Neurol Neurosurg Psychiatry. 2020 Mar;91(3):263-270. doi: 10.1136/jnnp-2019-321954. Epub 2020 Jan 14.
There are few validated fluid biomarkers in frontotemporal dementia (FTD). Glial fibrillary acidic protein (GFAP) is a measure of astrogliosis, a known pathological process of FTD, but has yet to be explored as potential biomarker.
Plasma GFAP and neurofilament light chain (NfL) concentration were measured in 469 individuals enrolled in the Genetic FTD Initiative: 114 expansion carriers (74 presymptomatic, 40 symptomatic), 119 mutation carriers (88 presymptomatic, 31 symptomatic), 53 mutation carriers (34 presymptomatic, 19 symptomatic) and 183 non-carrier controls. Biomarker measures were compared between groups using linear regression models adjusted for age and sex with family membership included as random effect. Participants underwent standardised clinical assessments including the Mini-Mental State Examination (MMSE), Frontotemporal Lobar Degeneration-Clinical Dementia Rating scale and MRI. Spearman's correlation coefficient was used to investigate the relationship of plasma GFAP to clinical and imaging measures.
Plasma GFAP concentration was significantly increased in symptomatic mutation carriers (adjusted mean difference from controls 192.3 pg/mL, 95% CI 126.5 to 445.6), but not in those with expansions (9.0, -61.3 to 54.6), mutations (12.7, -33.3 to 90.4) or the presymptomatic groups. GFAP concentration was significantly positively correlated with age in both controls and the majority of the disease groups, as well as with NfL concentration. In the presymptomatic period, higher GFAP concentrations were correlated with a lower cognitive score (MMSE) and lower brain volume, while in the symptomatic period, higher concentrations were associated with faster rates of atrophy in the temporal lobe.
Raised GFAP concentrations appear to be unique to -related FTD, with levels potentially increasing just prior to symptom onset, suggesting that GFAP may be an important marker of proximity to onset, and helpful for forthcoming therapeutic prevention trials.
在额颞叶痴呆（FTD）中，很少有经过验证的液体生物标志物。胶质纤维酸性蛋白（GFAP）是星形胶质细胞增生的一种衡量标准，而星形胶质细胞增生是 FTD 的一种已知病理过程，但尚未被探索为潜在的生物标志物。
在遗传 FTD 倡议中招募的 469 名个体中测量了血浆 GFAP 和神经丝轻链（NfL）浓度：114 个扩展携带者（74 个无症状，40 个有症状），119 个突变携带者（88 个无症状，31 个有症状），53 个突变携带者（34 个无症状，19 个有症状）和 183 个非携带者对照。使用线性回归模型，通过调整年龄和性别进行比较，将家族成员作为随机效应纳入其中。参与者接受了标准化的临床评估，包括简易精神状态检查（MMSE）、额颞叶变性-临床痴呆评定量表和 MRI。使用 Spearman 相关系数研究了血浆 GFAP 与临床和影像学测量值的关系。
症状性突变携带者的血浆 GFAP 浓度明显升高（与对照组相比，调整后的平均差异为 192.3pg/ml，95%CI 为 126.5 至 445.6），但扩张携带者（9.0，-61.3 至 54.6）、突变携带者（12.7，-33.3 至 90.4）或无症状携带者的 GFAP 浓度并未升高。在对照组和大多数疾病组中，GFAP 浓度与年龄呈显著正相关，与 NfL 浓度也呈正相关。在无症状期，较高的 GFAP 浓度与较低的认知评分（MMSE）和较低的脑容量相关，而在有症状期，较高的浓度与颞叶更快的萎缩速度相关。
升高的 GFAP 浓度似乎是 -相关 FTD 的特有表现，其水平可能在症状发作前升高，提示 GFAP 可能是发病临近的重要标志物，有助于即将进行的治疗性预防试验。
