White matter hyperintensities characterize monogenic frontotemporal dementia with granulin mutations

Area of Science:

• Neuroscience
• Genetics
• Neuropathology

Background:

• White matter hyperintensities (WMHs) are rarely reported in frontotemporal dementia (FTD).
• Previous studies identified WMHs in only 4 FTD cases with pathogenic Granulin (GRN) gene mutations.

Purpose of the Study:

• To investigate the presence and spatial distribution of WMHs in FTD patients with and without GRN mutations.
• To explore WMH burden in asymptomatic GRN mutation carriers.

Main Methods:

• Compared WMH burden and spatial distribution in FTD patients (GRN+ and GRN-), healthy controls (HC), and asymptomatic GRN+ subjects.
• Utilized automated WMH computation and voxelwise-based analysis.

Main Results:

• FTD-GRN+ patients exhibited significantly higher WMH burden than HC and FTD-GRN- groups.
• WMHs were predominantly located in the frontal, temporal, and parietal lobes.
• No significant WMH differences were found between asymptomatic GRN+ subjects and young healthy controls.

Conclusions:

• WMHs may represent a novel neurodegeneration mechanism in GRN-related FTD.
• Identifying WMHs could assist in the differential diagnosis of FTD.
• WMH findings may guide genetic screening for GRN mutations in FTD patients.