Cortical microstructure in familial frontotemporal dementia associated with MAPT, GRN, and C9orf72 pathogenic variants: Looking beyond atrophy - 31/10/25
, Pusheng Quan b, 1, ⁎ , Wencai Ding a, 1, ⁎ for the
ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) Research Consortium
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Abstract |
Background |
This study aimed to evaluate cortical mean diffusivity (cMD) as a sensitive biomarker for early neurodegenerative changes in familial frontotemporal lobar degeneration (FTLD) associated with C9orf72, GRN, and MAPT mutations. We compared cMD with cortical thickness (cTH) in detecting subtle microstructural alterations and examined its association with clinical severity and neurofilament light chain (NFL) concentrations.
Methods |
We analyzed data from 322 participants, including symptomatic carriers of C9orf72 (n = 85), GRN (n = 56), and MAPT (n = 58) mutations, along with 123 healthy controls. Cortical microstructure was assessed using both cTH and cMD. Clinical severity was evaluated with the CDR plus NACC FTLD scale, and plasma NFL was measured as a marker of neuroaxonal injury.
Results |
C9orf72 carriers exhibited the most widespread cortical thinning and increased cMD, while GRN and MAPT carriers showed more regionally restricted alterations. Across all mutation groups, cMD demonstrated higher sensitivity than cTH in detecting early changes. Furthermore, cMD values were significantly correlated with CDR plus NACC FTLD scores and NFL concentrations, underscoring its relevance to disease progression.
Conclusion |
Cortical mean diffusivity outperforms cortical thickness in detecting early microstructural changes in familial FTLD. Its strong association with both clinical severity and neurodegeneration biomarkers highlights its potential utility for early diagnosis, disease monitoring, and individualized therapeutic strategies in FTLD.
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Keywords : Biomarkers, Familial frontotemporal lobar degeneration, Cortical mean diffusivity, Neurofilament light chain, Early neurodegeneration
Plan
| ☆ | Data used in preparation of this article were obtained from the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) Research Consortium, As such, the investigators within the ALLFTD contributed to the design and implementation of ALLFTD and/or provided data but did not participate in analysis or writing of this report. |
Vol 12 - N° 10
Article 100306- décembre 2025 Retour au numéro
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