Biomarkers.

Area of Science:

• Neuroimaging
• Neurodegenerative Diseases
• White Matter Integrity

Background:

• White matter (WM) facilitates tau pathology spread but is also compromised by tau accumulation.
• Understanding the dynamic relationship between tau and WM is crucial for neurodegenerative disease research.

Purpose of the Study:

• To investigate the longitudinal associations between tau accumulation and white matter (WM) integrity.
• To explore potential sex differences in these relationships.

Main Methods:

• Utilized longitudinal diffusion MRI and flortaucipir PET data from 374 participants.
• Assessed WM integrity using neurite density index (NDI) in the inferior temporal-white matter (IT-WM) tract.
• Employed structural equation modeling (SEM) to analyze relationships between tau metrics and WM integrity.

Main Results:

• Baseline tau levels influenced the rate of subsequent tau accumulation, mediated by IT-WM integrity.
• Progressive tau accumulation was associated with a decline in IT-WM neurite density index (NDI).
• These relationships were more pronounced in males, who also showed greater vascular risk impact on WM health and higher rates of tau accumulation in females.

Conclusions:

• Intact white matter plays a mechanistic role in modulating tau accumulation.
• Deterioration of white matter is linked to increased rates of tau accumulation.
• Significant sex differences in the tau-WM relationship warrant further investigation.