Abnormal white matter integrity in healthy apolipoprotein E epsilon4 carriers

Area of Science:

• Neuroimaging
• Genetics
• Neurology

Background:

• Apolipoprotein E epsilon4 (ApoE4) is a significant genetic risk factor for Alzheimer's disease (AD).
• The underlying neurobiological mechanisms of ApoE4's risk are not fully understood.
• Early detection of AD-related brain changes is crucial for intervention.

Purpose of the Study:

• To investigate white matter integrity in the parahippocampal gyrus of healthy elderly ApoE4 carriers versus noncarriers.
• To explore potential preclinical neuroimaging markers associated with AD genetic risk.
• To assess the relationship between white matter diffusion and cerebral atrophy proxies.

Main Methods:

• Diffusion tensor imaging (DTI) was employed to measure diffusion anisotropy in parahippocampal white matter.
• Fractional anisotropy and radial diffusivity were quantified in relation to the anterior commissure-posterior commissure plane.
• Lateral ventricular and temporal horn volumes were measured as indicators of cerebral atrophy.

Main Results:

• ApoE4 carriers exhibited significantly lower fractional anisotropy in parahippocampal white matter compared to noncarriers.
• Elevated radial diffusivity was observed in the parahippocampal white matter of ApoE4 carriers.
• No significant differences in ventricular volumes were found between groups, and DTI measures were not modulated by atrophy.

Conclusions:

• Diffusion tensor imaging can detect preclinical white matter alterations in individuals with the ApoE4 genotype.
• These findings suggest DTI's potential as a sensitive tool for identifying early AD-related neurobiological changes.
• Subtle white matter changes may precede overt atrophy in the context of AD genetic risk.