Biomarkers

Area of Science:

• Neuroimaging
• Neurodegenerative Diseases
• White Matter Integrity

Background:

• Alzheimer's disease (AD) and Limbic-predominant Age-related TDP-43 Encephalopathy (LATE) are distinct neurodegenerative conditions presenting with similar memory loss.
• Previous studies indicated white matter (WM) alterations in AD and LATE, suggesting WM damage may contribute to disease pathology.
• This study investigates the longitudinal changes in WM integrity in early AD and LATE.

Purpose of the Study:

• To examine the two-year progression of white matter (WM) fiber bundle alterations in early Alzheimer's disease (AD) and Limbic-predominant Age-related TDP-43 Encephalopathy (LATE).
• To compare the rate of WM changes between AD patients, LATE patients, and healthy controls.
• To elucidate the role of WM damage in the progression of these neurodegenerative diseases.

Main Methods:

• Inclusion of 16 AD patients, 12 LATE patients, and 15 healthy controls, confirmed by clinical and biomarker criteria.
• Two 3-tesla MRI scans were acquired two years apart for all participants.
• Whole-brain and tract-based fixel-based analyses using multi-shell diffusion MRI were performed to assess WM fiber density and cross-section changes over time, controlling for age and sex.

Main Results:

• White matter (WM) fiber bundle damage progressed in both AD and LATE patient groups over the two-year period.
• Patients showed a more pronounced decline in WM integrity compared to controls, particularly in tracts connecting temporal, parietal, and frontal lobes (e.g., arcuate fasciculus, middle longitudinal fasciculus).
• Specific tracts showed differential progression: AD patients had greater decline in the cingulum and inferior longitudinal fasciculus, while LATE patients showed more decline in the superior longitudinal fasciculus.

Conclusions:

• White matter (WM) fiber bundle alterations are a progressive feature in both Alzheimer's disease (AD) and Limbic-predominant Age-related TDP-43 Encephalopathy (LATE).
• The rate of WM deterioration is significantly higher in patients with AD and LATE compared to healthy individuals.
• These findings underscore the critical role and progressive nature of WM damage in the pathophysiology of AD and LATE.