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Longitudinal diffusion tensor imaging correlates with amyloid burden in Down syndrome.

Lisette Gwendolyn LeMerise1, José Guerrero-Gonzalez1, Andrew McVea1

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Summary

Amyloid beta accumulation in adults with Down syndrome is linked to white matter changes over time. Diffusion tensor imaging and amyloid PET scans are sensitive tools for tracking these neurodegenerative changes.

Keywords:
Alzheimer's diseaseDown syndromeamyloid burdenamyloid positron emission tomographydiffusion magnetic resonance imagingdiffusion tensor imaginglinear modelinglongitudinalmultimodalrate of changetract‐based spatial statistics

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Area of Science:

  • Neuroimaging
  • Neurodegenerative Diseases
  • Down Syndrome Research

Background:

  • Adults with Down syndrome (DS) exhibit accelerated amyloid beta (Aβ) plaque accumulation compared to neurotypical individuals with Alzheimer's disease (AD).
  • White matter (WM) microstructure, assessed via diffusion tensor imaging (DTI), can reveal neurodegenerative changes in longitudinal studies.
  • This study explores the connection between DTI metrics and Aβ burden in individuals with DS across the AD continuum.

Purpose of the Study:

  • To investigate the relationship between longitudinal changes in white matter microstructure and amyloid beta burden in adults with Down syndrome.
  • To determine if DTI can serve as a sensitive biomarker for neurodegeneration associated with amyloid accumulation in DS.

Main Methods:

  • Longitudinal amyloid Pittsburgh compound B positron emission tomography (PET) and DTI data were collected from 35 adults with DS (ages 25-57).
  • Centiloid (CL) values and DTI parameters (anisotropy, diffusivity) were analyzed.
  • Tract-based spatial statistics and permutation analysis identified correlations between the rates of change in CL and DTI metrics.

Main Results:

  • Significant correlations were found between the longitudinal rates of change for DTI parameters and Aβ burden.
  • Key affected regions included the corpus callosum, corona radiata, and long-association fibers.
  • Longitudinal analyses revealed more significant regions of change compared to cross-sectional analyses.

Conclusions:

  • Amyloid beta burden is associated with widespread, longitudinal white matter microstructural alterations in adults with Down syndrome.
  • These findings suggest that white matter changes are integral to the process of amyloid accumulation in DS.
  • DTI and amyloid-PET imaging offer sensitive methods for tracking microstructural and pathological changes over time in DS.