Elevation in network dynamics amplifies amyloid-dependent tau pathology.

Area of Science:

• Neuroscience
• Biomarkers of Aging and Dementia
• Neuroimaging

Background:

• The relationship between brain network dynamics and Alzheimer's disease (AD) pathologies, including amyloid beta (Aβ) and tau, across different disease stages (Braak stages) is not well understood.
• Investigating these connections is crucial for understanding AD pathogenesis and progression.

Purpose of the Study:

• To investigate the association between brain network dynamics, Aβ and tau pathology, and cognitive status in a cohort of aging individuals.
• To explore how network switching rates relate to the accumulation of Aβ and tau and their impact on cognitive function.

Main Methods:

• A cross-sectional study involving 216 participants from the Translational Biomarkers of Aging and Dementia (TRIAD) cohort.
• Resting-state functional magnetic resonance imaging (rs-fMRI) was analyzed using a multilayer modularity algorithm to assess brain network dynamics.
• Participants were stratified based on amyloid and tau positron emission tomography (PET) biomarkers and Braak stages.

Main Results:

• Individuals with both Aβ and tau positivity exhibited significantly higher network switching rates compared to those negative for both.
• Network switching rates increased progressively with advancing Braak stages and correlated with Aβ and tau burden in specific brain networks (dorsal attention, sensorimotor).
• A significant interaction between network switching rate and Aβ burden was observed, synergistically accelerating tau accumulation in Braak stages III-V and correlating with cognitive severity.

Conclusions:

• Elevated brain network switching is associated with increased Aβ and tau pathology and cognitive deterioration in Alzheimer's disease.
• These findings suggest that increased network switching may exacerbate Aβ-related tau accumulation and cognitive decline, supporting a framework where network dynamics play a critical role in AD progression.