Biomarkers

Area of Science:

• Neuroimaging
• Biophysics
• Alzheimer's Disease Research

Background:

• Myelin degeneration is implicated in Alzheimer's Disease (AD), but quantifying these changes is challenging.
• Diffusion MRI and X-ray scattering offer complementary sensitivities to myelin structure.

Purpose of the Study:

• To utilize advanced diffusion MRI metrics and X-ray scattering to detect and quantify myelin degeneration in an ex vivo AD mouse model.
• To compare the sensitivity of diffusion MRI and X-ray scattering in detecting myelin changes in white and gray matter.

Main Methods:

• Acquisition of diffusion MRI and X-ray scattering data from hAPP mutant and wild-type mouse brains.
• Calculation of diffusion myelin-sensitive metrics (e.g., radial diffusivity, axonal water fraction) and quantitative myelin mapping using X-ray scattering.
• Non-linear registration to the Allen Atlas and statistical comparison of white and gray matter regions between groups.

Main Results:

• Diffusion MRI revealed myelin degeneration in white matter (corpus callosum, alveus) of AD mice, indicated by increased radial diffusivity and reduced axonal water fraction.
• X-ray scattering detected significantly lower myelin levels in the gray matter (cortex, thalamus) of AD mice.
• White matter changes were more pronounced with diffusion MRI, while gray matter changes were primarily detected by X-ray scattering.

Conclusions:

• Both diffusion MRI and X-ray scattering detected imaging changes indicative of compromised myelin levels in AD mouse brains.
• Diffusion MRI is more sensitive to white matter myelin degeneration, whereas X-ray scattering can detect myelin changes in gray matter where MRI sensitivity is limited.
• X-ray scattering shows promise for detecting subtle myelin degeneration in AD, particularly in gray matter regions.