Biomarkers

Area of Science:

• Neuroscience
• Neuropathology
• Radiology

Background:

• Non-amnestic Alzheimer's disease (AD) exhibits greater white matter (WM) degeneration than amnestic AD.
• Understanding the relationship between WM changes and AD pathophysiology is crucial for explaining earlier onset and atypical tau distribution in non-amnestic AD.
• This study hypothesizes that WM degeneration correlates with tau burden and grey matter atrophy in fiber tract endpoints, linking WM changes to tau progression.

Purpose of the Study:

• To investigate the relationship between white matter (WM) degeneration, tau burden, and grey matter atrophy in different Alzheimer's disease (AD) variants.
• To compare WM connectivity (using generalized fractional anisotropy - GFA and nodal degree) between amnestic and non-amnestic AD.
• To explore the association between tau deposition, regional atrophy, and WM integrity in individuals with AD.

Main Methods:

• Included 46 participants with normal cognition or AD, categorized into amnestic and various non-amnestic syndromes.
• Assessed tau burden using flortaucipir PET scans and WM integrity using diffusion MRI-derived GFA and nodal degree.
• Employed linear mixed effects models to analyze differences in GFA and nodal degree and tested associations between GFA and tau burden (SUVR) in tract endpoints.

Main Results:

• Non-amnestic AD showed significantly lower nodal degree, indicating sparser connectivity, though GFA did not differ between groups.
• Tau burden (SUVR) increased with higher atrophy tertiles across AD variants (p < 0.0001).
• WM integrity (GFA) was reduced in tracts connecting to areas of higher atrophy, and higher tau SUVR in cortical endpoints was associated with lower tractwise GFA (p < 0.0001).

Conclusions:

• Replicated findings of reduced WM connectivity in non-amnestic compared to amnestic AD.
• Demonstrated that WM integrity is associated with tau burden and atrophy in the endpoints of fiber tracts.
• Confirmed consistency of results across diverse non-amnestic syndromes, linking WM degeneration to core AD pathologies.