ORCID: https://orcid.org/0000-0002-0267-8590; Russell, Lucy L. ORCID: https://orcid.org/0000-0001-5023-5893; Foster, Phoebe H. ORCID: https://orcid.org/0000-0001-6300-6598; Ferry‐Bolder, Eve; Swieten, John C. van; Jiskoot, Lize C.; Seelaar, Harro; Sanchez‐Valle, Raquel; Laforce, Robert; Graff, Caroline; Galimberti, Daniela; Vandenberghe, Rik; Mendonça, Alexandre de ORCID: https://orcid.org/0000-0002-0488-1453; Tiraboschi, Pietro; Santana, Isabel; Gerhard, Alexander; Levin, Johannes; Nacmias, Benedetta; Otto, Markus; Bertoux, Maxime; Lebouvier, Thibaud; Butler, Chris R. ORCID: https://orcid.org/0000-0002-7502-9284; Ber, Isabelle Le; Finger, Elizabeth ORCID: https://orcid.org/0000-0003-4461-7427; Tartaglia, Maria Carmela ORCID: https://orcid.org/0000-0002-5944-8497; Masellis, Mario ORCID: https://orcid.org/0000-0002-6244-2096; Rowe, James B. ORCID: https://orcid.org/0000-0001-7216-8679; Synofzik, Matthis ORCID: https://orcid.org/0000-0002-2280-7273; Moreno, Fermin ORCID: https://orcid.org/0000-0001-5200-3164; Borroni, Barbara ORCID: https://orcid.org/0000-0001-9340-9814; Rohrer, Jonathan D. ORCID: https://orcid.org/0000-0002-6155-8417; Iturria‐Medina, Yasser und Ducharm, Simon
(2025):
White matter hyperintensities precede other biomarkers in GRN frontotemporal dementia.
In: Alzheimer's & Dementia, Bd. 21, Nr. 10, e70695
[PDF, 1MB]
Abstract
INTRODUCTION
Increased white matter hyperintensities (WMHs) have been reported in genetic frontotemporal dementia (FTD) in small studies, but the sequence of WMH abnormalities relative to other biomarkers is unclear.
METHODS
Using a large dataset (n = 763 GENFI2 participants), we measured WMHs and examined them across genetic FTD variants and stages. Cortical and subcortical volumes were parcellated, and serum neurofilament light chain (NfL) levels were measured. Biomarker progression was assessed with discriminative event-based and regression modeling.
RESULTS
Symptomatic GRN carriers showed elevated WMHs, primarily in the frontal lobe, while no significant increase was observed in symptomatic C9orf72 or MAPT carriers. WMH abnormalities preceded NfL elevation, ventricular enlargement, and cortical atrophy. Longitudinally, baseline WMHs predicted subcortical changes, while subcortical volumes did not predict WMH changes, suggesting WMHs may precede neurodegeneration.
DISCUSSION
WMHs are elevated in a subset of GRN-associated FTD. When present, they appear early and should be considered in disease progression models.
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| Fakultät: | Medizin > Munich Cluster for Systems Neurology (SyNergy) |
| Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
| URN: | urn:nbn:de:bvb:19-epub-129585-7 |
| ISSN: | 1552-5260 |
| Sprache: | Englisch |
| Dokumenten ID: | 129585 |
| Datum der Veröffentlichung auf Open Access LMU: | 19. Nov. 2025 12:45 |
| Letzte Änderungen: | 19. Nov. 2025 12:45 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
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