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Structural Brain Signature of FTLD Driven by Granulin Mutation
journal contribution
posted on 2023-06-08, 12:40 authored by Marco Bozzali, Valentina Battistoni, Enrico Premi, Antonella Alberici, Giovanni Giulietti, Silvana Archetti, Marinella Turla, Roberto Gasparotti, Mara Cercignani, Alessandro Padovani, Barbara BorroniSeveral causative gene mutations have been identified in frontotemporal lobar degeneration (FTLD), including mutations within Granulin (GRN) genes. It was recently shown that FTLD patients carriers of GRN Thr272fs mutation [FTLD-GRN(m+)] exhibit more severe abnormalities, as assessed by magnetic resonance imaging (MRI), than those with sporadic FTLD [FTLD-GRN(m-)]. The aim of this study was to investigate the relationship between grey (GM) and white matter (WM) microstructural damage in FTLD patients, carriers, and non-carriers of the mutation. Twenty-three FTLD patients [6 GRN(m+) and 17 GRN(m-)] and 12 healthy subjects received an MRI scan including volumetric and diffusion imaging. GM was assessed using voxel-based morphometry, while the corpus callosum was reconstructed using diffusion tractography. Mean diffusivity and fractional anisotropy of the corpus callosum were compared between groups. FTLD patients showed widespread GM atrophy and altered diffusion indices in the corpus callosum when compared to healthy subjects. When contrasting GRN(m+) against GRN(m-) patients, the former group had more atrophy in the left frontal GM, and reduced fractional anisotropy and increased mean diffusivity in the left anterior part of the corpus callosum. Significant correlations between the GM and WM damage were found in GRN(m+) patients. This pattern of damage was able to predict some of the additional neuropsychological deficits observed in GRN(m+) as compared to GRN(m-) patients. A more prominent involvement of WM in GRN(m+) patients is consistent with the knowledge that GRN genes are expressed in the microglia. This involvement might be responsible for the accrual of additional GM atrophy via disconnection mechanisms.
History
Publication status
- Published
Journal
Journal of Alzheimer's DiseaseISSN
1387-2877Publisher
IOS PressExternal DOI
Issue
2Volume
33Page range
483-494Department affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-10-18Usage metrics
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