Structural Connectivity in Down Syndrome and Alzheimer's Disease

Area of Science:

• Neuroscience
• Genetics
• Radiology

Background:

• Down syndrome (DS) results from trisomy 21, causing atypical neurodevelopment and amyloid precursor protein overproduction, leading to early Alzheimer's disease (AD).
• Research is shifting focus from neural loss to white matter neurodegeneration in AD, with DS serving as a model for predementia stages.

Purpose of the Study:

• To synthesize current research on in-vivo structural connectivity in individuals with Down syndrome.
• To investigate the impact of Alzheimer's disease on pre-existing white matter alterations in DS.
• To explore the functional significance and methodological considerations of these findings.

Main Methods:

• Review of exploratory studies utilizing magnetic resonance imaging (MRI)-based diffusion techniques.
• Characterization of in-vivo structural connectivity in young and older individuals with DS.

Main Results:

• White matter structures affected in DS include the corpus callosum and major long-association fibres (inferior fronto-occipital, inferior and superior longitudinal, uncinate fasciculus, cingulum bundle).
• The cingulum bundle and corpus callosum show particular sensitivity to early AD-related changes in the DS population.

Conclusions:

• Structural connectivity in Down syndrome is characterized by widespread white matter alterations.
• Specific white matter tracts, notably the corpus callosum and cingulum bundle, are vulnerable to early Alzheimer's disease pathology in individuals with DS.
• Further research is needed to understand the functional implications and refine methodologies.