Brain volumetric deficits in MAPT mutation carriers: a multisite study.

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Mutations in the MAPT gene are a known cause of frontotemporal dementia (FTD).
• Symptomatic MAPT mutation carriers exhibit frontotemporal atrophy.
• Previous research on presymptomatic carriers shows mixed results regarding gray matter volumes.

Purpose of the Study:

• To investigate whether presymptomatic MAPT mutation carriers have reduced structural brain volumes.
• To determine if these volume reductions occur in brain regions affected during the symptomatic phase of FTD.
• To utilize a voxelwise approach for detailed brain volumetrics analysis.

Main Methods:

• Voxel-based morphometry was performed on T1-weighted MRI images.
• The study included 22 symptomatic and 43 presymptomatic MAPT mutation carriers.
• Brain volumetrics were assessed across clinical subgroups, age, and mutation subtypes.

Main Results:

• Symptomatic carriers displayed gray matter atrophy in the frontotemporal cortex, insula, and striatum, and white matter atrophy in the corpus callosum and uncinate fasciculus.
• Approximately 20% of presymptomatic carriers showed reduced gray matter volumes in the hippocampus, amygdala, and lateral temporal cortex.
• These gray matter reductions were observed in presymptomatic carriers as early as their thirties, with white matter reductions being infrequent.

Conclusions:

• A subset of presymptomatic MAPT mutation carriers exhibit reduced mesial temporal lobe volumes, a region consistently atrophied in symptomatic individuals.
• The increasing prevalence of reduced mesial temporal volume with age in presymptomatic carriers suggests early-onset neurodegeneration.
• These findings highlight the potential for early detection and intervention in MAPT-mutation-associated FTD.