Investigating the role of neuroinflammation and brain clearance in frontotemporal lobar degeneration using 7T MRI and fluid biomarkers: protocol for a cross-sectional study in a tertiary care setting.
| Title: | Investigating the role of neuroinflammation and brain clearance in frontotemporal lobar degeneration using 7T MRI and fluid biomarkers: protocol for a cross-sectional study in a tertiary care setting. |
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| Authors: | Prinse FAM; 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.; van der Weerd L; C.J. Gorter Center for MRI, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.; van Swieten JC; Department of Neurology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.; Ronen I; Clinical Imaging Science Centre, Brighton and Sussex Medical School, Brighton, UK.; Seelaar H; Department of Neurology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.; Hirschler L; C.J. Gorter Center for MRI, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.; Najac C; C.J. Gorter Center for MRI, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.; Dopper EGP; Department of Neurology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands e.dopper@erasmusmc.nl. |
| Source: | BMJ open [BMJ Open] 2025 Aug 03; Vol. 15 (8), pp. e102668. Date of Electronic Publication: 2025 Aug 03. |
| Publication Type: | Clinical Trial Protocol; Journal Article |
| Language: | English |
| Journal Info: | Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101552874 Publication Model: Electronic Cited Medium: Internet ISSN: 2044-6055 (Electronic) Linking ISSN: 20446055 NLM ISO Abbreviation: BMJ Open Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : BMJ Publishing Group Ltd, 2011- |
| MeSH Terms: | Brain*/diagnostic imaging ; Brain*/metabolism ; Frontotemporal Lobar Degeneration*/diagnostic imaging ; Frontotemporal Lobar Degeneration*/cerebrospinal fluid ; Frontotemporal Lobar Degeneration*/metabolism ; Neuroinflammatory Diseases*/diagnostic imaging; Biomarkers/cerebrospinal fluid ; Biomarkers/blood ; Iron/metabolism ; Magnetic Resonance Imaging/methods ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cross-Sectional Studies ; Tertiary Care Centers ; Observational Studies as Topic ; Multicenter Studies as Topic |
| Abstract: | Introduction: 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.; Methods and Analysis: 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.; Ethics and Dissemination: 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.; Study Registration Number: NCT06870838; Pre-results.; (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.) |
| Competing Interests: | Competing interests: None declared. |
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| Contributed Indexing: | Keywords: Dementia; Neuroradiology |
| Molecular Sequence: | ClinicalTrials.gov NCT06870838 |
| Substance Nomenclature: | 0 (Biomarkers); E1UOL152H7 (Iron) |
| Entry Date(s): | Date Created: 20250803 Date Completed: 20250803 Latest Revision: 20250808 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12320043 |
| DOI: | 10.1136/bmjopen-2025-102668 |
| PMID: | 40754329 |
| Database: | MEDLINE |
Clinical Trial Protocol; Journal Article