Deep white matter in Huntington's disease.

Area of Science:

• Neuroimaging
• Neurodegenerative Diseases
• White Matter Microstructure

Background:

• White matter (WM) abnormalities are documented in both presymptomatic and symptomatic Huntington's disease (HD) using Magnetic Resonance Imaging (MRI).
• Understanding early microstructural changes in WM is crucial for identifying therapeutic targets in HD.

Purpose of the Study:

• To investigate the microstructure of long-range deep WM tracts in presymptomatic (Pre-HD) and symptomatic HD subjects.
• To compare WM integrity using Diffusion Tensor Imaging (DTI) and T2*-weighted imaging to assess iron levels.

Main Methods:

• Utilized DTI-based tractography and T2*-weighted imaging in 25 Pre-HD subjects, 25 HD patients, and 50 healthy controls.
• Analyzed axial diffusivity (AD), radial diffusivity (RD), fractional anisotropy (FA), and iron levels in deep WM tracts.

Main Results:

• Pre-HD subjects exhibited increased AD, RD, and iron levels compared to controls.
• WM integrity (FA) decreased from Pre-HD to HD phase, with further increases in AD/RD.
• Iron levels decreased in HD patients, suggesting failed remyelination attempts.

Conclusions:

• Presymptomatic HD subjects show early WM damage and attempt repair, indicated by increased iron levels, years before symptom onset.
• This repair mechanism is insufficient and fails with disease progression in symptomatic HD patients.
• WM degeneration in HD follows a distinct pattern, even in the presymptomatic stage.