Scientific article
Open access

Disease-related cortical thinning in presymptomatic granulin mutation carriers

Published inNeuroImage. Clinical, vol. 29, 102540
Publication date2021
First online date2020-12-29

Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical thickness (CTh) for each subject. We also perform a vertex-wise general linear model to assess differences between groups in the relationship between CTh and diverse covariables as gender, age, the estimated years to onset and education. We also explored differences according to TMEM106B genotype, a possible disease modifier. Whole brain CTh did not differ between carriers and noncarriers. Both groups showed age-related cortical thinning. The group-by-age interaction analysis showed that this age-related cortical thinning was significantly greater in GRN carriers in the left superior frontal cortex. TMEM106B did not significantly influence the age-related cortical thinning. Our results validate and expand previous findings suggesting an increased CTh loss associated with age and estimated proximity to symptoms onset in GRN carriers, even before the disease onset.

  • Cortical thickness
  • Frontotemporal dementia
  • GRN
  • Genetic mutations
  • Presymptomatic
  • Cerebral Cortical Thinning
  • Frontotemporal Dementia / diagnostic imaging
  • Frontotemporal Dementia / genetics
  • Granulins
  • Heterozygote
  • Humans
  • Membrane Proteins / genetics
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Progranulins
  • Medical Research Council - [MC_UU_00005/12]
  • Medical Research Council - [MR/M008525/1]
  • Medical Research Council - [MC_UU_00024/1]
  • Medical Research Council - [MR/M023664/1]
  • CIHR - [327387]
  • Medical Research Council - [MR/T046015/1]
  • Department of Health - [BRC149/NS/MH]
  • Medical Research Council - [MR/J009482/1]
  • Medical Research Council - [MC_U123160651]
  • Wellcome Trust - [103838]
  • Medical Research Council - [MR/K010395/1]
  • Medical Research Council - [MR/M018288/1]
  • Medical Research Council - [MC_U105597119]
  • Alzheimers Research UK - [ARUK-NAS2016B-2]
  • National Institute for Health Research (NIHR) - [NF-SI-0617-10175]
  • Dutch Research Council (NWO) - [056-13-018]
  • Wellcome Trust - Restoring brain function: from cortical microcircuits to complex behaviours in neurodegenerative disease. [103838]
  • European Commission - Solving the unsolved Rare Diseases [779257]
Citation (ISO format)
BORREGO-ÉCIJA, Sergi et al. Disease-related cortical thinning in presymptomatic granulin mutation carriers. In: NeuroImage. Clinical, 2021, vol. 29, p. 102540. doi: 10.1016/j.nicl.2020.102540
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Article (Published version)
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ISSN of the journal2213-1582

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Creation11/16/2022 10:38:58 AM
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