Prinse Fieke A M, van der Weerd Louise, van Swieten John C, Ronen Itamar, Seelaar Harro, Hirschler Lydiane, Najac Chloé, Dopper Elise G P
Department of Neurology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
C.J. Gorter Center for MRI, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
BMJ Open. 2025 Aug 3;15(8):e102668. doi: 10.1136/bmjopen-2025-102668.
Frontotemporal lobar degeneration (FTLD) is the second most common early-onset dementia. Several studies demonstrated that neuroinflammation and iron accumulation occur in FTLD. However, the timing and relevance of these processes and whether these two are merely cause or consequence remains unclear. Elucidating the role is crucial to assess the rationale for using anti-inflammatory therapies in FTLD. Additionally, the process of glymphatic brain clearance has gained attention as a potential contributor in the disease pathophysiology.
In this multimodal biomarker study, we use a combination of ultra-high field (7T) MR, blood and cerebrospinal fluid (CSF) biomarkers to investigate the role of neuroinflammation, iron accumulation and brain clearance in FTLD, and to identify biomarkers to differentiate FTLD-TDP from FTLD-tau. We aim to include 25 patients with probable FTLD-tau, 25 with probable FTLD-TDP and 50 healthy individuals with 50% risk to develop FTLD. We will use several MRI techniques, including magnetic resonance spectroscopy, diffusion weighted spectroscopy and quantitative susceptibility mapping. In addition, we will assess the prevalence of perivascular spaces (PVS) and the mobility of CSF to address glymphatic brain clearance. We will compare quantitative MR markers between patients with FTLD-tau and FTLD-TDP, presymptomatic mutation carriers and healthy controls, and correlate these measures with clinical data and biomarkers in blood and CSF.
We obtained ethical approval from the Medical Ethics Committee Leiden Den Haag Delft (NL78272.058.21). The results will be disseminated through presentations at national and international conferences, open-access peer-reviewed publications, ClinicalTrials.gov and to the public through social media posts and annual newsletters.
NCT06870838; Pre-results.
额颞叶变性（FTLD）是第二常见的早发性痴呆。多项研究表明，FTLD中存在神经炎症和铁蓄积。然而，这些过程的发生时间和相关性，以及这两者是仅仅作为病因还是结果尚不清楚。阐明其作用对于评估在FTLD中使用抗炎疗法的基本原理至关重要。此外，脑类淋巴系统清除过程作为疾病病理生理学中的一个潜在因素已受到关注。
在这项多模态生物标志物研究中，我们结合超高场（7T）磁共振成像、血液和脑脊液（CSF）生物标志物，以研究神经炎症、铁蓄积和脑清除在FTLD中的作用，并识别区分FTLD-TDP与FTLD-tau的生物标志物。我们旨在纳入25例可能为FTLD-tau的患者、25例可能为FTLD-TDP的患者以及50名有50%发生FTLD风险的健康个体。我们将使用多种磁共振成像技术，包括磁共振波谱、扩散加权波谱和定量磁化率映射。此外，我们将评估血管周围间隙（PVS）的患病率和脑脊液的流动性，以探讨脑类淋巴系统清除情况。我们将比较FTLD-tau和FTLD-TDP患者、症状前突变携带者和健康对照之间的定量磁共振标记物，并将这些测量结果与临床数据以及血液和脑脊液中的生物标志物进行关联。
我们获得了莱顿-代尔夫特-海牙医学伦理委员会（NL78272.058.21）的伦理批准。研究结果将通过在国内和国际会议上的报告、开放获取的同行评审出版物、ClinicalTrials.gov以及通过社交媒体帖子和年度通讯向公众传播。
NCT06870838；预结果。
