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Structural Brain Changes in Pre-Clinical FTD MAPT Mutation Carriers.

Clara Domínguez-Vivero1, Liwen Wu2, Seonjoo Lee2

  • 1Department of Neurology, Columbia University, Cognitive Neuroscience Division of the Taub Institute, G.H. Sergievsky Center, New York, NY, USA.

Journal of Alzheimer'S Disease : JAD
|April 21, 2020
PubMed
Summary
This summary is machine-generated.

Early brain changes in asymptomatic MAPT mutation carriers show specific temporal lobe, cingulate cortex, and lingual gyrus alterations, potentially serving as biomarkers for frontotemporal dementia (FTD) before symptoms appear.

Keywords:
AtrophyMAPT mutationbrain atrophyearly detectionfrontotemporal lobar degeneration

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Area of Science:

  • Neuroscience
  • Genetics
  • Radiology

Background:

  • Frontotemporal dementia (FTD) is a leading cause of early-onset neurodegenerative dementia.
  • Early imaging changes in FTD are often subtle, with widespread structural changes apparent only at later diagnostic stages.

Purpose of the Study:

  • To identify the earliest structural brain alterations in individuals carrying MAPT mutations before the onset of clinical symptoms.
  • To investigate preclinical changes in brain volume and white matter integrity in asymptomatic MAPT mutation carriers.

Main Methods:

  • A cross-sectional, multicenter study involving multiple generations from six families with five MAPT mutations.
  • Comparison of regional brain volumes and white matter integrity using advanced MRI sequences (DTI, ASL) in preclinical MAPT mutation carriers and controls.
  • Comprehensive assessments including medical exams, neuropsychological testing, and genetic analysis.

Main Results:

  • Significant correlations between mutation status and reduced volumes in specific brain regions: temporal lobe (amygdala, temporal pole), cingulate cortex (anterior and posterior cingulate), and lingual gyrus.
  • No significant differences were observed in overall brain volume, white matter hyperintensities, or white matter integrity via DTI.

Conclusions:

  • The temporal lobe, cingulate cortex, and lingual gyrus are identified as early affected areas in the preclinical stage of FTD.
  • These specific regional changes may serve as valuable biomarkers for FTD detection prior to the manifestation of overt clinical symptoms.