Soltaninejad, Mahdie;
Dadar, Mahsa;
Collins, D Louis;
Rajabli, Reza;
Venkatraghavan, Vikram;
Bouzigues, Arabella;
Russell, Lucy L;
... GENFI Consortium; + view all
(2025)
White matter hyperintensities precede other biomarkers in GRN frontotemporal dementia.
Alzheimer's & Dementia
, 21
(10)
, Article e70695. 10.1002/alz.70695.
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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. // Highlights: Elevated WMH volumes are found predominantly in symptomatic GRN. WMH accumulation is mostly observed in the frontal lobe. WMH abnormalities appear early in GRN-associated FTD, before NfL, atrophy, and ventriculomegaly. Longitudinally, WMH volumes can predict subcortical changes, but not vice versa. WMHs are key early markers in GRN-associated FTD and should be included in progression models.
| Type: | Article |
|---|---|
| Title: | White matter hyperintensities precede other biomarkers in GRN frontotemporal dementia |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.70695 |
| Publisher version: | https://doi.org/10.1002/alz.70695 |
| Language: | English |
| Additional information: | Copyright © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0/, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Biomarker sequence, C9orf72, dementia, disease progression, early marker, event-based modeling, FTD, GRN, MAPT, magnetic resonance imaging, neurodegeneration, neurofilament light chain, neuroimaging, progranulin, white matter |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10216415 |
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